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Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5‘ flanking region of the human insulin gene
Author(s) -
WEAVER J. U.,
KOPELMAN P. G.,
HITMAN G. A.
Publication year - 1992
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1992.tb01461.x
Subject(s) - insulin resistance , medicine , endocrinology , obesity , insulin , hyperinsulinemia , candidate gene , biology , diabetes mellitus , body mass index , allele , glucose homeostasis , genetics , gene
. presented to the European Association for the Study of Diabetes, September 1990 and the 6th International Congress on Obesity, October 1990 Abstract. Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non‐insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non‐diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin. An association of the class 3 allele of the hypervari‐able region in the 5′ flanking region of the insulin gene was found with upper segment obesity ( P =0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia ( P =0.01), stimulated insulin secretion ( P = 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P = 0.008). No such associations were found with the other candidate genes studied. This data suggests that polymorphisms in the 5′ flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.