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Introduction: The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance., Objective: The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus., Materials and Methods: In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry., Results: Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p = 0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found. These associations remained after adjustment using individual genetic admixture estimates., Conclusion: Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.

To determine whether there are variations in leptin levels according to the beta(3)-adrenoceptor (beta(3)-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826A-->G polymorphisms, given the regulatory role of catecholamines through the beta(3)-AR in leptin production and the previously reported association of the UCP1 -3826A-->G variant with obesity. A total of 160 men and 172 women randomly chosen from a nationwide population-based obesity cross-sectional survey in Spain were studied. Body mass index (BMI), waist-to-hip ratio (WHR), leptin, insulin, fasting and 2-hour post-glucose load glycemia, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, and total cholesterol, and triglyceride plasma levels were measured. beta(3)-AR Trp64Arg and UCP1 -3826A-->G genotypes were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). UCP1 -3826G allele frequency was higher in men than in women (0.31 v 0.22, P = .015) and in obese women than in non-obese women (0.31 v 0.17, P = .008). Women carriers of the Arg64 or the alleles also showed higher leptin levels than noncarriers. Multiple linear regression analysis showed that the Arg64 allele is associated with higher leptin levels after the adjustment for gender, age, WHR, and the degree of glucose tolerance. In conclusion, the beta(3)-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. Furthermore, our results agree with the previously reported association between UCP1 -3826G allele and obesity and point to a gender-related effect.