In this study, we investigated whether UCP2 -866G/A, Ala55Val and Ins/Del polymorphisms were associated with DKD in patients with type 2 diabetes mellitus (T2DM), and whether they had an effect on UCP2 gene expression in human kidney tissue biopsies.
Based on our case-control study and meta-analysis, we conclude that UCP2 Ala55Val and -866G/A polymorphisms are not significantly associated with type 2 diabetes risk in the Chinese population.
In our case-control study of people with European ancestry we were not able to demonstrate any association between the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.
In contrast, our results indicate that the UCP2 Ala55Val and UCP3 -55C/T polymorphisms may indeed be risk factors for susceptibility to type 2 diabetes in individuals of Asian descent, but not in individuals of European descent.
Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016).
These results indicate that the Ala55 --> Val and Ala232 --> Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.
In our case-control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 -866G/A, Ins/Del, Ala55Val and UCP3 -55C/T polymorphisms with obesity.
We examined the association of commonly observed UCP2 G(-866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population.
UCP2 A55V variant might predispose to obesity and Val55 allele to confer population-attributable risk for 9.5% of obese disorders and increase insulin concentrations.
No association was found between the Ala55Val SNP and obesity and blood levels of insulin, glucose, and lipids as well as blood pressure and circulating hormones.
These results indicate that the Ala55 --> Val and Ala232 --> Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.
The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort.
Thus, UCP2 rs659366 A allele and rs660339 T allele are both related to longer LTL in subjects without diabetes, independent of cardiovascular risk factors.
To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242).
We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects.
We examined the association of commonly observed UCP2 G(-866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population.
Recently, our group reported that the -866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of the UCP2 gene was associated with increased risk for DR in patients with DM.