DOCSLIB.ORG

Influence of Serum Amyloid a (SAA1) And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Influence of Serum Amyloid a (SAA1) And Influence of Serum Amyloid A (SAA1) and SAA2 Gene Polymorphisms on Renal Amyloidosis, and on SAA/ C-Reactive Protein Values in Patients with Familial Mediterranean Fever in the Turkish Population AYSIN BAKKALOGLU, ALI DUZOVA, SEZA OZEN, BANU BALCI, NESRIN BESBAS, REZAN TOPALOGLU, FATIH OZALTIN, and ENGIN YILMAZ ABSTRACT. Objective. To evaluate the effect of serum amyloid A (SAA) 1 and SAA2 gene polymorphisms on SAA levels and renal amyloidosis in Turkish patients with familial Mediterranean fever (FMF). Methods. SAA1 and SAA2 gene polymorphisms and SAA levels were determined in 74 patients with FMF (39 female, 35 male; median age 11.5 yrs, range 1.0–23.0). All patients were on colchicine therapy. SAA1 and SAA2 gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). SAA and C-reactive protein (CRP) values were measured and SAA/CRP values were calculated. Results. The median SAA level was 75 ng/ml (range 10.2–1500). SAA1 gene polymorphisms were: α/α genotype in 23 patients (31.1%), α/ß genotype in 30 patients (40.5%), α/γ genotype in one patient (1.4 %), ß/ß genotype in 14 patients (18.9%), ß/γ genotype in 5 patients (6.8 %), and γ/γ geno- type in one patient (1.4%). Of the 23 patients who had α/α genotype for the SAA1 polymorphism, 7 patients had developed renal amyloidosis (30.4%) compared to only one patient without this geno- type (1/51; 2.0%); p < 0.001. SAA2 had no effect on renal amyloidosis. SAA1 and SAA2 genotypes had no significant effect on SAA levels. SAA/CRP values were significantly lower in patients with the SAA1α/α genotype, compared to other SAA1 genotypes: 0.16 (0.025–1.96) versus 0.23 (0.012–28.20), p < 0.05. Conclusion. SAA1α/α genotype is one genetic factor that confers a significant risk for amyloidosis in the Turkish FMF population. Neither the SAA1 nor SAA2 genotypes had a significant effect on SAA level. (J Rheumatol 2004;31:1139–42) Key Indexing Terms: FAMILIAL MEDITERRANEAN FEVER AMYLOIDOSIS SERUM AMYLOID A POLYMORPHISM Familial Mediterranean fever (FMF) is a recessively inher- In 1997, 2 independent groups (French FMF Consortium ited disorder. The diagnosis is based on the occurrence of and International FMF Consortium) identified the gene recurrent episodes of fever and serous inflammation mani- responsible for FMF, designated MEFV, on chromosome 16 fested by sterile peritonitis, arthritis, and pleurisy. The (16p13.3)2,3. The most common MEFV mutations are disease primarily affects Sephardic Jews, Armenians, Turks, M694V, M680I, V726A, and M694I located on exon 10 and and North African Arabs. Amyloidosis of AA type, mainly E148Q located on exon 2. Genotype-phenotype correlation renal, is the major complication of FMF1. It develops over is not well established. There are unexplained ethnic differ- years and progresses to renal failure. ences in the rates of amyloidosis1,4-6. Although early data suggested that M694V mutation was a risk factor for From the Departments of Pediatrics, Pediatric Nephrology, and Medical amyloidosis, there are also patients with FMF who have Biology, and the Rheumatology Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey. renal amyloidosis and do not carry the M694V homozygous 7-10 A. Bakkaloglu, MD, Professor of Pediatrics; A. Duzova, MD, Assistant genotype . Unidentified genetic and environmental Professor of Pediatrics; S. Ozen, MD, Professor of Pediatrics; N. Besbas, factors might have a protective or exacerbating effect on MD, Professor of Pediatrics; R. Topaloglu, MD, Professor of Pediatrics; renal amyloidosis. F. Ozaltin, MD, Fellow in Pediatric Nephrology, Department of Pediatrics, Pediatric Nephrology and the Rheumatology Unit; B. Balci, Serum amyloid A (SAA) protein family is known to PhD; E. Yilmaz, PhD, Associate Professor of Medical Biology, contain a number of differentially expressed apolipoproteins Department of Medical Biology. that are synthesized primarily by the liver. The concentra- Address reprint requests to Dr. A. Bakkaloglu, Department of Pediatrics, tion of acute phase SAA can increase to more than 1000- Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey. 11 E-mail: [email protected] fold during inflammation . Its sensitivity was shown to be Submitted August 26, 2002; revision accepted January 6, 2004. equal or more than that of C-reactive protein (CRP) in Personal non-commercialPersonal, non-commercial use only. use The only. Journal The Journal of of RheumatologyRheumatology. Copyright Copyright© 2004. All rights © reserved. 2004. All rights reserved Bakkaloglu, et al: SAA gene polymorphisms 1139 Downloaded on October 4, 2021 from www.jrheum.org several studies; persistently high SAA levels were correlated SAA measurement. SAA levels were measured by solid phase sandwich with activity of rheumatic disease, rapid progression of ELISA method (Cytoscreen, Human SAA immunoassay kit; Biosource secondary amyloidosis, and poor outcome in patients under- International, Camarillo, CA, USA). The normal SAA level was < 10 ng/ml. Blood samples for SAA and CRP measurements were drawn at least 12,13 going certain surgical interventions . 2 weeks after an FMF attack. This period was chosen since we aimed to Acute phase isotypes of human SAA are encoded at 2 measure subclinical inflammation in these patients and not levels during an different loci, SAA1 and SAA2. SAA3 is a pseudogene14. It attack. The SAA/CRP ratio was calculated. has been suggested that AA-fibrils deposited in tissues were Analysis of polymorphisms in SAA1 and SAA2 genes. The SAA1 α, ß, and predominantly derived from SAA1α15. SAA1 and SAA2 are γ isoforms are encoded by the V52-A57, A52-V57, and A52-A57 SAA1 α serum precursors of amyloid A1 (AA1) and A2 (AA2) alleles, respectively. The SAA2 and ß isoforms are encoded by the H71 and R71 SAA2 alleles. These polymorphisms are located in the coding proteins, the principal components of the secondary amyloid region of the gene. SAA1 and SAA2 gene polymorphisms were analyzed plaques. Although prolonged high plasma levels of SAA using polymerase chain reaction-restriction fragment length polymorphism may lead to the deposition of its products, AA proteins, in (PCR-RFLP), as described23. SAA2 gene polymorphism was available in tissues, high concentrations of SAA are not sufficient to 69 patients. promote the development of amyloidosis. Recent studies Statistical analysis. Results were expressed as median (minimum- have focused on the polymorphisms of SAA as the genetic maximum) for data not showing normal distribution and as mean ± stan- 16-18 dard deviation (SD) for data showing normal distribution. Mann-Whitney background for amyloidogenesis . U and chi-squared tests were used for comparison. P values < 0.05 were Recently, Cazeneuve, et al showed in a group of considered significant. Armenian patients with FMF that the SAA1α/α genotype was associated with a 7-fold increased risk for renal amyloi- RESULTS dosis, compared with other SAA1 genotypes19. No correla- Clinical features, MEFV mutation analysis, and distribution tion with SAA levels was examined. of SAA1 and SAA2 gene polymorphisms are summarized in There is continuous subclinical inflammation in patients Table 1. Median age at onset of clinical symptoms was 3 with FMF20. Our group has previously shown that FMF (0.5–13) years, median age at diagnosis was 7 (1–16) years. patients homozygous and compound heterozygous for The mean duration of FMF was 7.5 ± 4.40 years (range MEFV mutation had higher SAA levels compared to 1–15) and duration of colchicine prophylaxis 3.50 ± 3.64 heterozygotes21. Elevated SAA levels in FMF patients can years (range 1–13). Colchicine dosage ranged from 0.5 to be secondary to either subclinical inflammation or to SAA1 genotype. It is well known that CRP correlates markedly with SAA in most inflammatory disorders, and that no study Table 1. Clinical characteristics, MEFV mutation analysis, and SAA1 and has reported the effect of a genetic factor in producing a SAA2 gene polymorphisms of 74 patients with FMF. variation in serum CRP levels. The SAA/CRP ratio can be a Features n (%) useful measure when evaluating the relation between SAA values and SAA1 genotypes in patients with continuous M/F 35/39 inflammation22. Current age, yrs median, (minimum-maximum) 11.5 (1–23) We evaluated the influence of SAA1 and SAA2 poly- Amyloidosis 8/74 (10.8) Consanguinity 20/74 (27.0) morphisms on renal amyloidosis, SAA level, and SAA/CRP Family history 34/74 (45.9) values in Turkish patients with FMF. History of appendectomy 7/74 (9.5) Clinical features MATERIALS AND METHODS Fever 70/74 (94.6) Patients. SAA1 and SAA2 gene polymorphisms and SAA levels were Abdominal pain 69/74 (93.2) determined in 74 FMF patients (39 female, 35 male; median age 11.5 yrs, Pleurisy 34/74 (45.9) range 1.0–23.0) who were homozygous or compound heterozygous for Arthritis/arthralgia 59/74 (69.7) MEFV mutation (M694V, M694I, M680I, V726A, and E148Q). MEFV mutations Homozygous or compound heterozygous patients were recruited in order to M694V/M694V 44/74 (59.5) clarify the effect of MEFV genotype on SAA level21. M694V/M680I 21/74 (28.4) The clinical data were registered on a standardized form that included M694V/V726A 9/74 (12.2) age, sex, familial consanguinity, history of the disease, age at onset of SAA1 genotypes α α symptom(s), presence of fever, abdominal pain, pleurisy, joint pain, duration / 23/74 (31.1) α of FMF disease, duration of colchicine prophylaxis, and colchicine dosage. /ß 30/74 (40.5) α γ All patients were on colchicine therapy and drug compliance was estimated / 1/74 (1.4) to be good. Informed consent was obtained from the patient or the parents. ß/ß 14/74 (18.9) ß/γ 5/74 (6.8) Mutation analysis.
Load more

Recommended publications
  • Cellular and Plasma Proteomic Determinants of COVID-19 and Non-COVID-19 Pulmonary Diseases Relative to Healthy Aging
    RESOURCE https://doi.org/10.1038/s43587-021-00067-x Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging Laura Arthur1,8, Ekaterina Esaulova 1,8, Denis A. Mogilenko 1, Petr Tsurinov1,2, Samantha Burdess1, Anwesha Laha1, Rachel Presti 3, Brian Goetz4, Mark A. Watson1, Charles W. Goss5, Christina A. Gurnett6, Philip A. Mudd 7, Courtney Beers4, Jane A. O’Halloran3 and Maxim N. Artyomov1 ✉ We examine the cellular and soluble determinants of coronavirus disease 2019 (COVID-19) relative to aging by performing mass cytometry in parallel with clinical blood testing and plasma proteomic profiling of ~4,700 proteins from 71 individuals with pul- monary disease and 148 healthy donors (25–80 years old). Distinct cell populations were associated with age (GZMK+CD8+ T cells and CD25low CD4+ T cells) and with COVID-19 (TBET−EOMES− CD4+ T cells, HLA-DR+CD38+ CD8+ T cells and CD27+CD38+ B cells). A unique population of TBET+EOMES+ CD4+ T cells was associated with individuals with COVID-19 who experienced moderate, rather than severe or lethal, disease. Disease severity correlated with blood creatinine and urea nitrogen levels. Proteomics revealed a major impact of age on the disease-associated plasma signatures and highlighted the divergent contri- bution of hepatocyte and muscle secretomes to COVID-19 plasma proteins. Aging plasma was enriched in matrisome proteins and heart/aorta smooth muscle cell-specific proteins. These findings reveal age-specific and disease-specific changes associ- ated with COVID-19, and potential soluble mediators of the physiological impact of COVID-19.
    [Show full text]
  • Paediatric Rheumatology Are MEFV Mutations Susceptibility Factors In
    Paediatric rheumatology Are MEFV mutations susceptibility factors in enthesitis-related arthritis patients in the eastern Mediterranean? B. Gülhan1, A. Akkuş1, L. Özçakar2, N. Beşbaş1, S. Özen1 1Department of Paediatric Nephrology ABSTRACT ILAR, with an aim to also cover the and Rheumatology, and Objective. Enthesitis-related arthritis previously suggested terms of juvenile 2 Department of Physical and Rehabilitation, (ERA), is a complex genetic disease. spondyloarthropathy and seronegative Hacettepe University Faculty of Medicine, Although HLA-B27 is well established, enthesitis arthritis syndrome (1, 2). The Ankara, Turkey. it does not explain all the genetic load etiopathogenesis of ERA is not certain Bora Gülhan, MD in ERA. Familial Mediterranean fe- however, it is a complex genetic disease Abdulkadir Akkuş, MD Levent Özçakar, MD ver (FMF), caused by mutations in the like the other subtypes of JIA. Genetic Nesrin Beşbaş, MD MEFV gene, is a frequent autoinflam- predisposition has a significant impact Seza Özen, MD matory disorder in the eastern Medi- on ERA, where common single nucleo- Please address correspondence to: terranenan. tide polymorphisms in multiple genes Prof. Seza Özen, Methods. We investigated the clini- are contributory as well, with real but Department of Paediatrics, cal and imaging features of 53 ERA variable environmental components. Faculty of Medicine, patients, as well as the frequency of HLA-B27 accounts for the major Hacettepe University, MEFV gene mutations in those who genetic load and is positive in approxi- 06100 Sıhhiye, Ankara, Turkey. were HLA-B27 negative. E-mail: [email protected] mately 90% of the patients with juve- Results. The mean age of the patients nile ankylosing spondylitis (AS) (3).
    [Show full text]
  • A A20, 156–157, 386, 423 AB12, 326 ABCA1 Transporter, 395 Abelson
    Index A AGI-5198, 218 A20, 156–157, 386, 423 AhR-KO mice, 417 AB12, 326 AIM2, 85 ABCA1 transporter, 395 Aiolos (IKZF3), 179 Abelson murine leukemia virus (A-MuLV), AKAP450, 204 165, 193 Akt, 424, 445 ABL, 472 Alarmin, 119–120, 430 ABO blood type, 98 Aldehyde dehydrogenase 1 (ALDH1), 187 Abscopal effect, 463 ALK1, 243 ACE-KO mice, 410 Allo-antibodies, 100 Acetylcholine (Ach), 127 Allogenic, 306 Acetyl-CoA (coenzyme A), 211 Allograft, 306 Activated protein C (rhAPC), 454 α-ketoglutarate (α-KG), 215 Adalimumab, 356 α-linoleic acid (ALA), 458 ADAM10, 109, 263, 335 α 1, 3 galactosyltransferase, 98 ADAM12, 264, 416 α 1, 3 N-acetylgalactosaminyl (GalNAc) ADAM15, 264 transferase, 98 ADAM17, 152, 264, 275 α7 nAchR, 397 ADAMTS1, 264, 265 α smooth muscle actin (α-SMA), 235 ADAMTS2, 265 Alpha2 plasmin inhibitor (α2PI), 59 ADAMTS9, 265 Alzheimer’s disease, 110 ADAMTS13, 265 AMD3100, 360, 405 Adenine nucleotide translocase (ANT), 206 Amelanotic melanoma cells, 454 Adenylate cyclase, 397 American Society of Clinical Oncology Adherens junction (AJ), 42, 249, 473 (ASCO), 437 Adhesion, 42 Ammonia, 363 Adipose tissue, 332, 383–384 AMP-activated protein kinase (AMPK), 214, A Disintegrin and Metalloprotease (ADAM), 216, 373 253 Amyloid fibrils, 110 Adjuvant, 122 Amyloid precursor protein (APP), 110 Advanced bladder cancer, 189 Anakinra (IL-1ra), 154 Advanced glycation end product (AGE), 109 Anaphylatoxins, 30 AE3-208, 429, 458 Anchorage-independent three-dimensional Aggregation, 59 growth, 194 Aggresome, 393 Androgen receptor (AR), 224 © Springer Japan 2016
    [Show full text]
  • BMC Medical Genomics Biomed Central
    BMC Medical Genomics BioMed Central Research article Open Access Hepatic inflammation mediated by hepatitis C virus core protein is ameliorated by blocking complement activation Ming-Ling Chang*1, Chau-Ting Yeh1, Deng-Yn Lin1, Yu-Pin Ho1, Chen- Ming Hsu1 and D Montgomery Bissell2 Address: 1Liver Research Center and Department of Hepatogastroenterology, Chang Gung Memorial Hospital; Chang Gung University, College of Medicine, Taoyuan, Taiwan, Republic of China and 2Liver Center and Department of Medicine, University of California, San Francisco, San Francisco, CA, USA Email: Ming-Ling Chang* - [email protected]; Chau-Ting Yeh - [email protected]; Deng- Yn Lin - [email protected]; Yu-Pin Ho - [email protected]; Chen-Ming Hsu - [email protected]; D Montgomery Bissell - [email protected] * Corresponding author Published: 8 August 2009 Received: 11 July 2008 Accepted: 8 August 2009 BMC Medical Genomics 2009, 2:51 doi:10.1186/1755-8794-2-51 This article is available from: http://www.biomedcentral.com/1755-8794/2/51 © 2009 Chang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The pathogenesis of inflammation and fibrosis in chronic hepatitis C virus (HCV) infection remains unclear. Transgenic mice with constitutive HCV core over-expression display steatosis only. While the reasons for this are unclear, it may be important that core protein production in these models begins during gestation, in contrast to human hepatitis C virus infection, which occurs post-natally and typically in adults.
    [Show full text]
  • Mass Spectrometric Determination of the Effect of Surface Deactivation on Membranes Used for In-Situ Sampling of Cerebrospinal Fluid (CSF)
    Supplementary Materials Mass Spectrometric Determination of the Effect of Surface Deactivation on Membranes Used for In-Situ Sampling of Cerebrospinal Fluid (CSF) Torgny Undin 1, Andreas P Dahlin 2, Jonas Bergquist 1, and Sara Bergström Lind 1,* 1 Department of Chemistry-BMC, Analytical Chemistry, Uppsala University, PO Box 599, SE-751 24 Uppsala, Sweden; [email protected] (T.U.); [email protected] (J.B.) 2 Department of Engineering Sciences, Uppsala University, PO Box 534, SE-751 21 Uppsala, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-18-4713693 Supplementary Table Table A Heat map of identified adsorbed proteins on coated membranes in group A. A time resolved map of all identified proteins that adsorbs to the surface providing deeper information about the adsorption behavior of the individual proteins compared to the more schematic Fig. 2. The three colors in the heat map indicate zero (white), one (light green) or two or more (dark green) unique peptides identified for a particular protein. A protein must be identified by two peptides at least one time point to be considered identified. Protein 15 30 60 120 240 480 Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 - [CO3_HUMAN] 2 2 2 2 2 2 Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 - [ALBU_HUMAN] 2 2 2 2 2 2 Coagulation factor V OS=Homo sapiens GN=F5 PE=1 SV=4 - [FA5_HUMAN] 2 2 2 2 2 2 Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=2 - [CO4A_HUMAN] 2 2 2 2 2 2 Clusterin OS=Homo sapiens GN=CLU PE=1 SV=1 - [CLUS_HUMAN] 2 2 2 2 2 2 Fibulin-1
    [Show full text]
  • Acute-Phase Serum Amyloid a Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study
    Cardiovascular and Metabolic Risk ORIGINAL ARTICLE Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study 1,2 6 CAROLA MARZI, MPH H.-ERICH WICHMANN, MD, PHD ype 2 diabetes is preceded by a 2,3 4,7 CORNELIA HUTH, PHD MICHAEL RODEN, MD 4 2,3 differential activation of compo- CHRISTIAN HERDER, PHD ANNETTE PETERS, PHD T 2,3 1,2 nents of the innate immune system JENS BAUMERT, PHD HARALD GRALLERT, PHD 2,3 8 (1,2). Serum amyloid A (SAA) is a sensi- BARBARA THORAND, PHD WOLFGANG KOENIG, MD 5 1,9 tive marker of the acute inflammatory WOLFGANG RATHMANN, MD THOMAS ILLIG, PHD 2,3 CHRISTA MEISINGER, MD state. Its acute-phase isoform (A-SAA) is up-regulated up to 1,000-fold in response to inflammatory stimuli such as trauma, – OBJECTIVEdWe sought to investigate whether elevated levels of acute-phase serum amyloid infection, injury, and stress (3 5). The A (A-SAA) protein precede the onset of type 2 diabetes independently of other risk factors, high inductive capacity, along with the including parameters of glucose metabolism. fact that genes and proteins are highly conserved throughout the evolution of RESEARCH DESIGN AND METHODSd Within the population-based Cooperative vertebrates and invertebrates, suggests Health Research in the Region of Augsburg (KORA) S4 study, we measured A-SAA concentrations that A-SAA plays a key role in pathogen in 836 initially nondiabetic subjects (55–74 years of age) without clinically overt inflammation who participated in a 7-year follow-up examination including an oral glucose tolerance test.
    [Show full text]
  • Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review
    Journal of Clinical Medicine Article Amyloid Goiter in Familial Mediterranean Fever: Description of 42 Cases from a French Cohort and from Literature Review Hélène Vergneault 1 , Alexandre Terré 1, David Buob 2,†, Camille Buffet 3 , Anael Dumont 4, Samuel Ardois 5, Léa Savey 1, Agathe Pardon 6,‡, Pierre-Antoine Michel 7, Jean-Jacques Boffa 7,†, Gilles Grateau 1,† and Sophie Georgin-Lavialle 1,*,† 1 Internal Medicine Department and National Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA), APHP, Tenon Hospital, Sorbonne University, 4 rue de la Chine, 75020 Paris, France; [email protected] (H.V.); [email protected] (A.T.); [email protected] (L.S.); [email protected] (G.G.) 2 Department of Pathology, APHP, Tenon Hospital, Sorbonne University, 4 rue de la Chine, 75020 Paris, France; [email protected] 3 Thyroid Pathologies and Endocrine Tumor Department, APHP, Pitié-Salpêtrière Hospital, Sorbonne University, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; [email protected] 4 Department of Internal Medicine, Caen University Hospital, Avenue de la Côte de Nacre, 14000 Caen, France; [email protected] 5 Department of Internal Medecine, Rennes Medical University, 2 rue Henri le Guilloux, 35000 Rennes, France; [email protected] 6 Dialysis Center, CH Sud Francilien, 40 Avenue Serge Dassault, 91100 Corbeil-Essonnes, France; [email protected] 7 Citation: Vergneault, H.; Terré, A.; Department of Nephrology, APHP, Tenon Hospital, 4 rue de la Chine, 75020 Paris, France; [email protected] (P.-A.M.); [email protected] (J.-J.B.) Buob, D.; Buffet, C.; Dumont, A.; * Correspondence: [email protected]; Tel.: +33-156016077 Ardois, S.; Savey, L.; Pardon, A.; † Groupe de Recherche Clinique amylose AA Sorbonne Université- GRAASU.
    [Show full text]
  • Diversity and Complexity of the Mouse Saa1 and Saa2 Genes
    Exp. Anim. 63(1), 99–106, 2014 —Original— Diversity and Complexity of the Mouse Saa1 and Saa2 genes Masayuki MORI1), Geng TIAN1), Akira ISHIKAWA2), and Keiichi HIGUCHI1) 1)Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, 3–1–1 Asahi, Matsumoto, Nagano 390-8621, Japan 2)Laboratory of Animal Genetics, Division of Applied Genetics and Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan Abstract: Mouse strains show polymorphisms in the amino acid sequences of serum amyloid A 1 (SAA1) and serum amyloid A 2 (SAA2). Major laboratory mouse strains are classified based on the sequence as carrying the A haplotype (e.g., BALB/c) or B haplotype (e.g., SJL/J) of the Saa1 and Saa2 gene unit. We attempted to elucidate the diversity of the mouse Saa1 and Saa2 family genes at the nucleotide sequence level by a systematic survey of 6 inbred mouse strains from 4 Mus subspecies, including Mus musculus domesticus, Mus musculus musculus, Mus musculus castaneus, and Mus spretus. Saa1 and Saa2 genes were obtained from the mouse genome by PCR amplification, and each full-length nucleotide sequence was determined. We found that Mus musculus castaneus mice uniquely possess 2 divergent Saa1 genes linked on chromosome 7. Overall, the mouse strains had distinct composite patterns of amino acid substitutions at 9 positions in SAA1 and SAA2 isoforms. The mouse strains also had distinct composite patterns of 2 polymorphic upstream regulatory elements that influenced gene transcription in in vitro reporter assays. B haplotype mice were revealed to possess an LTR insertion in the downstream region of Saa1.
    [Show full text]
  • Gene Expression Signature for Biliary Atresia and a Role for Interleukin-8
    SUPPLEMENTARY “PATIENTS AND METHODS” “Gene expression signature for biliary atresia and a role for Interleukin-8 in pathogenesis of experimental disease” Bessho K, et al. PATIENTS AND METHODS Patients. Liver biopsies, serum samples and clinical data were obtained from infants with cholestasis enrolled into a prospective study (ClinicalTrials.gov Identifier: NCT00061828) of the NIDDK-funded Childhood Liver Disease Research and Education Network (www.childrennetwork.org) or from infants evaluated at Cincinnati Children’s Hospital Medical Center. For subjects with biliary atresia (BA), liver biopsies were obtained from 64 infants during the preoperative workup or at the time of intraoperative cholangiogram, with ages ranging from 22-169 days after birth (Supplementary Table 7). For subjects with intrahepatic cholestasis (serving as diseased controls, and referred to as non- BA), liver biopsy samples were obtained percutaneously or intraoperatively from 14 infants at the time of diagnostic evaluation, with ages ranging from 19-189 days. Their diagnosis were Alagille syndrome (N=1), multidrug resistance protein-3 deficiency (N=2), alpha-1-antitrypsin deficiency (N=2) and cholestasis with unknown etiology (N=9) (Supplementary Table 7). Representative liver biopsy photomicrographs are shown in Supplementary Figure 6A-D. A third group of normal controls (NC) consisted of liver biopsy samples obtained from 7 deceased-donor children aged 22-42 months as described previously (1). This group serves as a reference cohort, with the median levels of gene expression used to normalize gene expression across all patients in the BA and non-BA groups. This greatly facilitates the visual identification of key differences in gene expression levels between BA and non-BA groups.
    [Show full text]
  • The Expression of Genes Contributing to Pancreatic Adenocarcinoma Progression Is Influenced by the Respective Environment – Sagini Et Al
    The expression of genes contributing to pancreatic adenocarcinoma progression is influenced by the respective environment – Sagini et al Supplementary Figure 1: Target genes regulated by TGM2. Figure represents 24 genes regulated by TGM2, which were obtained from Ingenuity Pathway Analysis. As indicated, 9 genes (marked red) are down-regulated by TGM2. On the contrary, 15 genes (marked red) are up-regulated by TGM2. Supplementary Table 1: Functional annotations of genes from Suit2-007 cells growing in pancreatic environment Categoriesa Diseases or p-Valuec Predicted Activation Number of genesf Functions activationd Z-scoree Annotationb Cell movement Cell movement 1,56E-11 increased 2,199 LAMB3, CEACAM6, CCL20, AGR2, MUC1, CXCL1, LAMA3, LCN2, COL17A1, CXCL8, AIF1, MMP7, CEMIP, JUP, SOD2, S100A4, PDGFA, NDRG1, SGK1, IGFBP3, DDR1, IL1A, CDKN1A, NREP, SEMA3E SERPINA3, SDC4, ALPP, CX3CL1, NFKBIA, ANXA3, CDH1, CDCP1, CRYAB, TUBB2B, FOXQ1, SLPI, F3, GRINA, ITGA2, ARPIN/C15orf38- AP3S2, SPTLC1, IL10, TSC22D3, LAMC2, TCAF1, CDH3, MX1, LEP, ZC3H12A, PMP22, IL32, FAM83H, EFNA1, PATJ, CEBPB, SERPINA5, PTK6, EPHB6, JUND, TNFSF14, ERBB3, TNFRSF25, FCAR, CXCL16, HLA-A, CEACAM1, FAT1, AHR, CSF2RA, CLDN7, MAPK13, FERMT1, TCAF2, MST1R, CD99, PTP4A2, PHLDA1, DEFB1, RHOB, TNFSF15, CD44, CSF2, SERPINB5, TGM2, SRC, ITGA6, TNC, HNRNPA2B1, RHOD, SKI, KISS1, TACSTD2, GNAI2, CXCL2, NFKB2, TAGLN2, TNF, CD74, PTPRK, STAT3, ARHGAP21, VEGFA, MYH9, SAA1, F11R, PDCD4, IQGAP1, DCN, MAPK8IP3, STC1, ADAM15, LTBP2, HOOK1, CST3, EPHA1, TIMP2, LPAR2, CORO1A, CLDN3, MYO1C,
    [Show full text]
  • Spectrum of MEFV Variants and Genotypes Among Clinically Diagnosed FMF Patients from Southern Lebanon
    medical sciences Article Spectrum of MEFV Variants and Genotypes among Clinically Diagnosed FMF Patients from Southern Lebanon 1, 1, 1 2 1, Ali El Roz y , Ghassan Ghssein y, Batoul Khalaf , Taher Fardoun and José-Noel Ibrahim * 1 Faculty of Public Health, Lebanese German University (LGU), Sahel Alma 25136, Lebanon; [email protected] (A.E.R.); [email protected] (G.G.); [email protected] (B.K.) 2 Mashrek Medical Diagnostic Center, Tyre 62111, Lebanon; [email protected] * Correspondence: [email protected]; Tel.: +961-70-68-31-79 These authors contributed equally to this work. y Received: 30 May 2020; Accepted: 23 July 2020; Published: 17 August 2020 Abstract: Background: Familial Mediterranean Fever (FMF) is an autosomal recessive auto-inflammatory disease characterized by pathogenic variants in the MEFV gene, with allele frequencies greatly varying between countries, populations and ethnic groups. Materials and methods: In order to analyze the spectrum of MEFV variants and genotypes among clinically diagnosed FMF patients from South Lebanon, data were collected from 332 participants and 23 MEFV variants were screened using a Real-Time PCR Kit. Results: The mean age at symptom onset was 17.31 13.82 years. The most prevalent symptoms were abdominal pain, fever and myalgia. ± MEFV molecular analysis showed that 111 patients (63.79%) were heterozygous, 16 (9.20%) were homozygous, and 47 (27.01%) carried two variants or more. E148Q was the most encountered variant among heterozygous subjects. E148Q/M694V was the most frequent in the compound heterozygous/complex genotype group, while M694I was the most common among homozygous patients.
    [Show full text]
  • Human Serum Amyloid a (SAA)
    Clinical and Inflammation Research Area Human serum amyloid A (SAA) erum amyloid A recombinant SAA as well as purified endogenous apolipoprotein SAA has a tendency to aggregate and form oligomers Sfamily consists of (4-6). Presumably, the association of SAA molecules three members that in is mediated by amino acid residues located within human beings are cod- α-helix regions 1 (residues 2-8) and 3 (residues ed by different genes: 52-59) (4). SAA1, SAA2, and SAA4 (reviewed in 1-3). SAA1 The biological function of SAA and SAA2 are so-called acute phase isoforms. The biological function of SAA in inflammation is Their expression is in- unclear. It has been suggested that SAA is involved creased in response to in the recycling of cholesterol from damaged tissues. inflammation. SAA4 is It might play the role of a signaling molecule that a constitutive isoform, redirects HDL particles to activated macrophages the expression of which does not change during an and mediates the removal of stored cholesterol from acute-phase response. In addition, one more related them. Released cholesterol is then transferred to HDL gene (SAA3) has been identified, although this gene to be used again in the membranes of new cells that are is not expressed in human beings. required during acute inflammation and tissue repair (7). Besides that, published studies demonstrate Biochemical properties of SAA that recombinant SAA exhibits significant proinflammatory activity by inducing the synthesis SAA1 and SAA2 are synthesized in the liver of several cytokines and promoting chemotaxis for and secreted to the blood. When in the blood, monocytes and neutrophils in vitro (1, 8).
    [Show full text]