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A Genetic Variant of the CAPN10 Gene in Mexican Subjects With Nutr Hosp. 2014;30(3):671-677 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Original / Otros A genetic variant of the CAPN10 gene in Mexican subjects with dyslipidemia is associated with increased HDL-cholesterol concentrations after the consumption of a soy protein and soluble fiber dietary portfolio Martha Guevara-Cruz1, Nimbe Torres1, Armando R. Tovar1, M Elizabeth Tejero2, Ashley Castellanos-Jankiewicz2,3 and Laura del Bosque-Plata2* 1Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, DF. bLaboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, México, DF. cEscuela de Nutrición, Universidad Anáhuac Mayab, Mérida, México. México. Abstract UNA VARIANTE GENÉTICA DEL GEN CAPN10 EN SUJETOS MEXICANOS CON DISLIPIDEMIA Dyslipidemia is a major public health problem, and SE ASOCIA CON UN AUMENTO DE LAS therefore, it is important to develop dietary strategies CONCENTRACIONES DE COLESTEROL HDL to diminish the prevalence of this disorder. It was re- DESPUÉS DEL CONSUMO DE UN PORTAFOLIO cently reported that diet may play an important role in DIETARIO DE DE SOYA Y FIBRA SOLUBLE triggering insulin resistance by interacting with gene- tic variants at the CAPN10 gene locus in patients with metabolic syndrome. Nonetheless, it remains unknown Resumen whether genetic variants of genes involved in the develo- Dyslipidemia is a major public health problem, and pment of type 2 diabetes are associated with variations in therefore, it is important to develop dietary strategies high-density lipoprotein cholesterol (HDL-C). The study to diminish the prevalence of this disorder. It was re- used a single-center, prospective, cohort design. Here, we cently reported that diet may play an important role in CAPN10 assessed the effect of four variants of the gene triggering insulin resistance by interacting with gene- on HDL-C levels in response to a soy protein and soluble tic variants at the CAPN10 gene locus in patients with fiber dietary portfolio in subjects with dyslipidemia. In metabolic syndrome. Nonetheless, it remains unknown 31 Mexican dyslipidemic individuals, we analyzed four whether genetic variants of genes involved in the develo- CAPN10 gene variants (rs5030952, rs2975762, rs3792267, pment of type 2 diabetes are associated with variations in and rs2975760) associated with type 2 diabetes. Subjects high-density lipoprotein cholesterol (HDL-C). The study with the GG genotype of the rs2975762 variant of the used a single-center, prospective, cohort design. Here, we CAPN10 gene were better responders to dietary interven- assessed the effect of four variants of the CAPN10 gene tion, showing increased HDL-C concentrations from the on HDL-C levels in response to a soy protein and soluble first month of treatment. HDL-C concentrations in par- fiber dietary portfolio in subjects with dyslipidemia. In ticipants with the wild type genotype increased by 17.0%, 31 Mexican dyslipidemic individuals, we analyzed four whereas the HDL-C concentration in subjects with the CAPN10 gene variants (rs5030952, rs2975762, rs3792267, variant genotypes increased by only 3.22% (p = 0.03); the and rs2975760) associated with type 2 diabetes. Subjects low-density lipoprotein cholesterol levels of GG carriers with the GG genotype of the rs2975762 variant of the tended to decrease (-12.6%). These results indicate that CAPN10 gene were better responders to dietary interven- Mexican dyslipidemic carriers of the rs2975762-GG ge- tion, showing increased HDL-C concentrations from the notype are better responders to this dietary intervention. first month of treatment. HDL-C concentrations in parti- (Nutr Hosp. 2014;30:671-677) cipants with the wild type genotype increased by 17.0%, whereas the HDL-C concentration in subjects with the DOI:10.3305/nh.2014.30.3.7611 variant genotypes increased by only 3.22% (p = 0.03); the Key words: Calpain-10, polymorphism, dietary portfolio, low-density lipoprotein cholesterol levels of GG carriers hypercholesterolemic, dyslipidemia. tended to decrease (-12.6%). These results indicate that Mexican dyslipidemic carriers of the rs2975762-GG ge- notype are better responders to this dietary intervention. (Nutr Hosp. 2014;30:671-677) Correspondence/Correspondencia: Laura del Bosque-Plata. DOI:10.3305/nh.2014.30.3.7611 Mailing address: Periferico Sur 4809, Arenal Tepepan, Tlalpan, 14610. Ciudad de Mexico, Distrito Federal. Palabras clave: Calpain-10, polymorphism, dietary port- Email addres: [email protected] folio, hypercholesterolemic, dyslipidemia. Recibido: 20-V-2014. Aceptado: 28-VI-2014. 671 027_7611 A genetic variant of the CAPN10.indd 671 10/09/14 16:01 Introduction ponse to a dyslipidemia dietary treatment based on a soy protein and soluble fiber dietary portfolio. Dyslipidemia in Mexican adults is most commonly associated with low plasma levels of high-density li- poprotein cholesterol (HDL-C), which is often related Materials and Methods to the development of diseases classified as metabolic syndrome (MetS)1. The levels of plasma lipids are con- Study design trolled by multiple pathways and influenced by com- plex interactions between many different genes and The studied population was selected from a pre- environmental factors such as diet composition2. vious study3. The study used a single-center, prospec- A low saturated fat diet (LSF) in combination with tive, cohort design. Medical examination was perfor- soy protein and soluble fiber can improve the lipid med each month on all subjects. One nutritionist was profile of Mexican subjects with hyperlipidemia3 in- assigned for the follow-up of every 10 patients. Body dependent of genetic variants involved in lipid meta- weight and height were measured according to stan- bolism. Low-density lipoprotein cholesterol (LDL-C) dardize methods to calculate the total energy intake is reported to be positively associated with the risk of for each patient. Patients were given an LSF diet in myocardial infarction, whereas HDL-C has an inverse accordance with the National Cholesterol Education association4. LDL-C and HDL-C are among the most Program Adult Treatment Panel III (ATPIII) for four commonly measured biomarkers of cardiovascular weeks (Period 1)5. For the next two months, patients disease risk in clinical medicine5, and lower levels of were instructed to consume an LSF and dietary portfo- HDL-C have been consistently associated with an in- lio consisting of 25 g of soy protein and 15 g of soluble creased risk of coronary heart disease (CHD)6. Recent fiber (LSF-SSF diet) (Period 2). Body weight was mo- studies have shown that LSF, in combination with soy nitored during the study, and blood samples were co- protein and soluble fiber, can increase HDL-C levels llected after a 12-h overnight fasting period once every in the Mexican population with the ABCA1 (ATP-bin- month for three months. Nutritionists maintained con- ding cassette cholesterol transporter A1) R230C va- tact with the subjects twice per week and assessed their riant7, which appears to be exclusive to Native Ame- dietary consumption using the 24-h recall method and ricans8. a standard scale. Approximately 74% of the Mexican population with MetS has low a HDL-C concentration and a higher predisposition to develop type 2 diabetes mellitus9. Study population Nonetheless, it is not known whether genetic variants of genes involved in the development of diabetes are Thirty-one hyperlipidemic participants (15 males associated with low HDL-C. and 16 females) who completed the three-month die- The Calpain-10 (CAPN10) gene is located on chro- tary protocol were included in the study. The partici- mosome 2q37 and encodes for a cytoplasmic cysteine pants had no history of cardiovascular, renal, or liver protease that requires calcium ions for its activity. In disease, no history of type 2 diabetes or hypertension, mice, CAPN10 plays an important role in regulating had no smoking or alcohol consumption history, and obesity and type 2 diabetes10. This gene has attracted were not taking hypolipidemic agents. Subjects were considerable attention because of the association be- asked to maintain their habitual level of physical ac- tween calpain genetic variation and type 2 diabetes in tivity throughout the study. All subjects were fully in- humans11-13. CAPN10 has been associated with various formed of the protocol, and written informed consent risk factors of MetS, such as elevated body mass index was obtained. This study was approved by the Commi- (BMI)14, plasma cholesterol concentration15, hyper- ttee of Studies in Humans at the Instituto Nacional de tension 16, 17 and hypertriglyceridemia18, and plays an Ciencias Médicas y Nutrición Salvador Zubirán. important role in insulin resistance19. It has been su- ggested that CAPN10 facilitates the translocation of insulin-regulated glucose transporter type 4 (GLUT4) Biochemical assays by the reorganization of the cytoskeleton20. Variations in the CAPN10 gene are associated with elevated tri- A 5-ml blood sample was obtained after a 12-h fas- glyceride levels and reduced expression of CAPN10 ting period each month. Blood was centrifuged at 400 in the adipose tissue of obese subjects18. Variations in x g, and serum was separated and kept at −20 °C un- CAPN10 confer a risk for type 2 diabetes in several po- til analysis. Serum was analyzed for total cholesterol pulations, including those of Mexican origin14-17, 21-23. (TC), triglyceride (TG), and HDL-C. TC and TG were However, it is not known whether subjects with va- determined using an enzymatic assay (SERA-PAK riants of the CAPN10 gene would respond to dietary Plus, Bayer de México, Mexico City). Serum HDL-C treatments to improve HDL-C levels. Thus, the aim of was determined using an immunoassay method24 this study was to analyze the effects of variations in (DiaSys Diagnostics Systems GmbH, Holzheim, Ger- CAPN10 on HDL-C levels in Mexican adults in res- many), and LDL-C was calculated using the method 672 Nutr Hosp. 2014;30(3):671-677 Martha Guevara-Cruz et al.
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