A haplotype at the UCP1 gene locus contributes to genetic risk for type 2 diabetes in Asian Indians (CURES-72).
BACKGROUND
The gene encoding for uncoupling protein-1 (UCP1) is considered to be a candidate gene for type 2 diabetes because of its role in thermogenesis and energy expenditure. The objective of the study was to examine whether genetic variations in the UCP1 gene are associated with type 2 diabetes and its related traits in Asian Indians.


METHODS
The study subjects, 810 type 2 diabetic subjects and 990 normal glucose tolerant (NGT) subjects, were chosen from the Chennai Urban Rural Epidemiological Study (CURES), an ongoing population-based study in southern India. The polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies.


RESULTS
The three polymorphisms, namely -3826A-->G, an A-->C transition in the 5'-untranslated region (UTR) and Met229Leu, were not associated with type 2 diabetes. However, the frequency of the A-C-Met (-3826A-->G-5'UTR A-->C-Met229Leu) haplotype was significantly higher among the type 2 diabetic subjects (2.67%) compared with the NGT subjects (1.45%, P < 0.01). The odds ratio for type 2 diabetes for the individuals carrying the haplotype A-C-Met was 1.82 (95% confidence interval, 1.29-2.78, P = 0.009).


CONCLUSIONS
The haplotype, A-C-Met, in the UCP1 gene is significantly associated with the increased genetic risk for developing type 2 diabetes in Asian Indians.
Vimaleswaran
Karani S
KS
Madras Diabetes Research Foundation, Gopalapuram, Chennai-86, India.
Radha
Venkatesan
V
Ghosh
Saurabh
S
Majumder
Partha P
PP
Rao
M R S
MR
Mohan
Viswanathan
V
D000273:Adipose Tissue / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007194:India; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000502:physiology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D005947:Glucose