ARE POLYMORPHIC VARIANTS OF LEPTIN RECEPTOR GENE ASSOCIATED WITH DIABETES?

Northwestern University, Evanston IL

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Abstract

Obesity is a major health problem that is associated with co-morbid conditions, including diabetes mellitus (DM). Women with a history of gestational DM (GDM) are enriched for an increased BMI. For several reasons, we have hypothesized that women with GDM share a unique set of genetic characteristics apart from other presentations of type II DM. Moreover, the increase in BMI in this population may represent a phenotypic manifestation of the genotype that predisposes women to GDM. The proposed studies are designed to address this issue by examining the hypothesis that there is an association between GDM and population variants of the leptin receptor gene. These studies will be conducted using three groups of participants: (i) women with a history of GDM, (ii) BMI- and age-matched controls without GDM, and (iii) lean, age-matched controls without GDM. The frequency of 3 known polymorphisms in the leptin receptor gene and short tandem repeat polymorphisms associated with a microsatellite maker near the leptin receptor gene will then be determined within each group. If a specific polymorphism is present with increased frequency in the group with GDM, it would suggest a possible association between the leptin receptor gene and GDM. In addition, multiple phenotypic characteristics will be determined, including: (i)oral glucose tolerance, (ii) fasting insulin and leptin levels, (iii) body mass index, (iv) percent body fat, (v) pulse and blood pressure, and (vi) resting energy expenditure. Within each group, the phenotypic characteristics will be compared in those individuals with and without the specific polymorphisms to determine whether one of the polymorphisms is associated with an alteration of a specific phenotypic characteristic(s).