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(12) Patent Application Publication (10) Pub. No.: US 2012/0258183 A1 Smith Et Al US 20120258183A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0258183 A1 Smith et al. (43) Pub. Date: Oct. 11, 2012 (54) MACRONUTRIENT SENSITIVITY Publication Classification (51) Int. Cl. (76) Inventors: Graeme John Smith, Victoria CI2O I/68 (2006.01) C40B 40/06 (2006.01) (AU); Nick Argyrou, Victoria (AU); A2.3L I/00 (2006.01) Helen Argyrou, Victoria (AU); A6IP3/08 (2006.01) Harry Banaharis, Prahram (AU) A6IP3/06 (2006.01) C40B 30/00 (2006.01) (21) Appl. No.: 13/501867 A636/7 (2006.01) (52) U.S. Cl. .............. 424/726; 435/6.11:506/7:506/16; 426/2 (22) PCT Fled: Oct. 18, 2010 (57) ABSTRACT The present invention relates to a method and a kit for iden (86) PCT NO.: PCT/AU2O1 O/OO1384 tifying a Subjects macronutrient sensitivity. The method involves assaying a genetic sample from the Subject to deter S371 (c)(1), mine a polymorphism profile, analysing the polymorphism (2), (4) Date: Jun. 29, 2012 profile to identify risk alleles and determining the macronu trient sensitivity based on the number of risk alleles present. This information can be used for determining an appropriate (30) Foreign Application Priority Data diet to induce Satiety, formulating a diet for inducing Satiety, or for treating a range of medical complaints associated with Oct. 16, 2009 (AU) ................................ 2009905061 metabolism. US 2012/02581 83 A1 Oct. 11, 2012 MACRONUTRIENT SENSITIVITY 0010 Previous methods for the diagnosis and/or treatment of metabolic disorders linked to genetic polymorphisms or FIELD genotypes have focused on analysing a single gene putatively involved with the regulation of metabolism to determine 0001. The invention relates to a method for identifying a whether an individual is Susceptible to increased appetite. macronutrient sensitivity of a Subject. The invention also However, previous methods have failed to account for satiety, relates to a method for formulating a diet for inducing Satiety which is the physiological feedback mechanism Suppressing and a method for determining Satiety in a Subject. Further appetite. Therefore, a need exists for an alternative or more, the invention relates to a kit suitable for use in the improved method for the diagnosis and/or treatment of a methods of the invention. metabolic disorder linked to a genetic polymorphism, specifi cally accounting for Satiety. BACKGROUND 0011. It is to be understood that if any prior art publication 0002 Food is composed of three macronutrients and is referred to herein such reference does not constitute an numerous micronutrients. The three macronutrients are car admission that the publication forms a part of the common bohydrate, lipid and protein, whereas the micronutrients general knowledge in the artin Australia or any other country. comprise a variety of compounds including trace minerals and vitamins. SUMMARY 0003 Anthropological studies have suggested that an evo 0012. A first aspect provides a method for identifying a lutionary adaptation to a specific food type may be behind the Subject's macronutrient sensitivity, comprising the steps of different responses to diet between individuals. In some parts assaying a genetic sample from the Subject for a polymor of the world the ancient natural diet may have been more phism in a gene selected from the group consisting of meat-based and individuals descended from Such groups may TCF7L2(1), TCF7L2(2), KIR6.2(KCJN11), PPARG, be more suited to a high-protein, low-carbohydrate diet. In IGF2BP2, CDKN2B, FTO, SLC30A8, HHEX, CDKAL1, other parts of the world the ancient natural diet may have been WFS1, NOTCH2, JAZF1, CDC123, G6PC2, APOA5(1), more plant-based or grain-based and individuals descended APOA5(2) APOE, APOB(1), APOB(2), PSRC1, LDLR, from Such origins may be more Suited to a high-carbohydrate, CETP(1), CETP(2), LPL(1), LPL(2), PCSK9, FABP2, LEPR low-fat diet. (1) and LEPR(2) or combination thereof, to determine a poly 0004. It has been proposed also that a scarcity of a particu morphism profile, analysing said polymorphism profile to lar macronutrient in the ancient natural diet may have led to identify risk alleles and determining the macronutrient sen genetic adaptations that enable macronutrient metabolite sitivity of said subject based on the number of risk alleles turnover to be altered in order to retain systemically more of present. that macronutrient. Accordingly, it has been postulated that 0013 The identification of a subject's macronutrient sen the body evolved over time to treat the scarce macronutrient sitivity allows the provision of a diet plan taking into account as precious and to harvest as much of it as possible whenever this macronutrient sensitivity to allow the subject to achieve it was available. optimal satiety for initiating and maintaining weight loss, 0005. The modern Western diet provides unlimited access reducing body fat, ameliorating metabolic syndrome, to all of the macronutrients and thus these ancient adaptations improving health and well being, and managing food intol are no longer required. In fact, since the human body has not erance, for example. evolved to cope with such abundance of all of the macronu 0014. The method may provide an integrated approach to trients, such adaptations can be detrimental to an individual. satiety by accounting for both the genetic profile of the sub 0006 Most people adhering to a Western diet consume a ject and the most appropriate macronutrient composition for similar macronutrient profile. Despite this, there are highly the subject that will respond to the subject's genetic profile. varied responses to Such a diet, with systemic accumulation 0015. In one embodiment, the method comprises assaying of particular macronutrients leading to pathological conse a genetic sample from the Subject for at least one polymor quences in Some individuals and not in others. Some of the phism in each of 2,3,4,5,6,7,8,9, 10, 11, 12, 13, 14, 15, 16 pathologies associated with inappropriate macronutrient or 17 genes selected from the group consisting of TCF7L2(1), accumulation are obesity, insulin resistance, leptin resistance, TCF7L2(2), KIR6.2 (KCJN11), PPARG, IGF2BP2, type II diabetes and Sugar addiction, and complications asso CDKN2B, FTO, SLC30A8, HHEX, CDKAL1, WFS1, ciated with each. NOTCH2, JAZF1, CDC123, G6PC2, APOA5(1) and APOA5 0007. Historically, diets designed for weight loss and/or (2). health improvement have been based largely on actively 0016. In another embodiment, the method comprises enforced caloric restriction, or caloric restriction combined assaying a genetic sample from the Subject for at least one with lipid reduction and carbohydrate increase. These diets polymorphism in each of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 have been largely unsuccessful in addressing the problem of genes selected from the group consisting of APOE, APOB(1), weight loss and/or reduction in overall body fat as they are APOB(2), PSRC1, LDLR, CETP(1), CETP(2), LPL(1), LPL extremely difficult for the subject to maintain. (2), PCSK9, FABP2, LEPR(1), and LEPR(2). 0008 Weight loss, and maintenance of weight loss over 0017. In yet another embodiment, the method comprises time, can differ substantially between individuals. It has been assaying a genetic sample from the Subject for at least one suggested that this difference may result from differences polymorphism in each of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, between individuals at the genetic level. 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 0009. There is a clinically established genetic relationship 30 genes selected from the group consisting of TCF7L2(1), between obesity and metabolic disorders. This relationship TCF7L2(2), KIR6.2 (KCJN11), PPARG, IGF2BP2, may be caused by single-gene or multi-gene patterns of inher CDKN2B, FTO, SLC30A8, HHEX, CDKAL1, WFS1, itance. NOTCH2, JAZF1, CDC123, G6PC2, APOA5(1), APOA5(2), US 2012/02581 83 A1 Oct. 11, 2012 APOE, APOB(1), APOB(2), PSRC1, LDLR, CETP(1), IGF2BP2, CDKN2B, FTO, SLC30A8, HHEX, CDKAL1, CETP(2), LPL (1), LPL(2), PCSK9, FABP2, LEPR(1), and WFS1, NOTCH2, JAZF1, CDC123, G6PC2, APOA5(1), LEPR(2). APOA5(2), APOE, APOB(1), APOB(2), PSRC1, LDLR, 0018. The polymorphism may be a single nucleotide poly CETP(1), CETP(2), LPL (1), LPL(2), PCSK9, FABP2, morphism (SNP). LEPR(1), and LEPR(2) or combination thereof, to determine 0019. The method may comprise the step of assaying the a polymorphism profile, and formulating a diet based on that genetic sample to determine a haplogroup. The step of assay polymorphism profile. ing the genetic sample to determine a haplogroup may com 0030. A fourth aspect of the invention provides a kit, com prise assaying a mitochondrial polymorphism or a Y-chromo prising a genetic sampler for obtaining a genetic sample from Some polymorphism. a Subject, when the genetic sample is assayed according to the 0020. In one embodiment, the method comprises the step method of the first aspect. of calculating a score from the polymorphism profile. The 0031. A fifth aspect of the invention provides a kit for method may also comprise the step of determining the macro identifying a macronutrient sensitivity of a Subject, compris nutrient sensitivity based on the score. ing a reagent for assaying a genetic sample obtained from the 0021. The macronutrient sensitivity identified by the Subject for a polymorphism in a gene selected from the group method can be non-sensitive, carbohydrate sensitive, lipid consisting of TCF7L2(1), TCF7L2(2), KIR6.2 (KCJN11), sensitive or carbohydrate and lipid sensitive. PPARG, IGF2BP2, CDKN2B, FTO, SLC30A8, HHEX, 0022. In a particular embodiment, the genetic sample of CDKAL1, WFS1, NOTCH2, JAZF1, CDC123, G6PC2, the method is a buccal sample. APOA5(1), APOA5(2), APOE, APOB(1), APOB(2), PSRC1, 0023.
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