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.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Lakka
H M
HM
Research Institute of Public Health, University of Kuopio, Kuopio, Finland.
Oksanen
L
L
Tuomainen
T P
TP
Kontula
K
K
Salonen
J T
JT
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012307:Risk Factors
D002352:Carrier Proteins; D007328:Insulin; C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin