The common pentanucleotide polymorphism of the3 '-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
Hm. Lakka et al., The common pentanucleotide polymorphism of the3 '-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 M, 248(1), 2000, pp. 77-83
Citations number
32
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Objectives. The purpose of the study was to test whether the pentanucleotid
e 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 populat
ion-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 ca
ses and the controls came from a cohort of 985 men who had no diabetes at b
aseline.
Results. There was one homozygote and 22 heterozygotes for the 3'-UTR inser
tion 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 we
re homozygous for the deletion allele (P = 0.005). In a logistic regression
model adjusting for four strongest non-matched predictors of type 2 diabet
es, 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 lep
tin signalling system could contribute to serum insulin levels and the deve
lopment of type 2 diabetes.