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The common pentanucleotide polymorphism of the
3′‐untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non‐diabetic men: a prospective case–control study
Author(s) -
Lakka H.M.,
Oksanen L.,
Tuomainen T.P.,
Kontula K.,
Salonen J. T.
Publication year - 2000
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1046/j.1365-2796.2000.00696.x
Subject(s) - medicine , endocrinology , diabetes mellitus , type 2 diabetes , leptin , insulin , allele , population , leptin receptor , obesity , gene , biology , genetics , environmental health
. Lakka H‐M, Oksanen L, Tuomainen T‐P, Kontula K, Salonen JT (University of Kuopio, Kuopio, and the University of Helsinki, Helsinki, Finland). The common pentanucleotide polymorphism of the 3′‐untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non‐diabetic men: a prospective case–control study. J Intern Med 2000; 248: 77–83. Objectives. The purpose of the study was to test whether the pentanucleotide insertion/deletion polymorphism in the 3′‐untranslated region (3′‐UTR) of the leptin receptor gene, which has previously been associated with serum insulin levels in obese subjects, is associated with insulin levels and the risk of type 2 diabetes in non‐diabetic middle‐aged men. Subjects and design. We studied these associations in a prospective population‐based nested case–control study in 41 men who developed type 2 diabetes during 4‐year follow‐up and 81 controls who were matched for age, obesity, baseline glucose and insulin and other strongest risk factors. Both the cases and the controls came from a cohort of 985 men who had no diabetes at baseline. Results. There was one homozygote and 22 heterozygotes for the 3′‐UTR insertion allele amongst all 122 men. The carrier frequency of this allele was 9.8% amongst the cases and 23.5% amongst the controls. At baseline, the mean fasting serum insulin was 12.2 mU L –1 in the 23 men who were heterozygous or homozygous for the insertion allele and 17.1 mU L –1 in the 99 men who were homozygous for the deletion allele ( P = 0.005). In a logistic regression model adjusting for four strongest non‐matched predictors of type 2 diabetes, the carriers of the insertion allele had a 79% reduced risk of diabetes (OR = 0.21; 95% CI = 0.06–0.77, P = 0.019), compared with non‐carriers. Conclusion. Our findings support the hypothesis that alterations in the leptin signalling system could contribute to serum insulin levels and the development of type 2 diabetes.