Relationship between A-3826G polymorphism in the promoter of the uncoupling protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals: A cross-sectional study

Background. A-3826G polymorphism within the promoter region of the uncoupling protein-1 (UCP-1) gene is possibly involved in the pathophysiology of obesity and metabolic disorders. However, the effects of UCP-1 A-3826G polymorphism on high-density lipoprotein cholesterol (HDL-C), a major contributor to atherosclerotic disease, still have not been established. Methods. A total of 298 healthy Japanese subjects (144 males and 154 females, mean age: 45.2 years) with a body mass index (BMI) of 20.0-30.0 kg/m(2), regular lifestyles, and receiving no medication were enrolled in the cross-sectional study to estimate the relationship of serum HDL-C levels with UCP-1 A-3826G polymorphism by genomic PCR and Bcl1-restriction fragment length polymorphism analysis. We used 1.04 mmol/L of HDL-C in Japanese males and 1.29 mmol/L in Japanese females as cut-off values of low HDL-cholesterolemia. Results. The genotype and allele frequencies of UCP-1 A-3826G polymorphism were similar to those previously reported in the Japanese population. In males, HDL-C levels of the GG genotype (1.75 +/- 0.49 mmol/L) were significantly higher than those found in the AA genotype (1.45 +/- 0.34 mmol/L, p = 0.0 15). In females, the occurrence rate of low HDL-cholesterolemia was significantly different by genotype: a low prevalence in the GG genotype (15.4% in the AA 4.8% in the AG, 15.4% in the GG genotype, p = 0.022). Logistic regression analysis was used to identify risk factors for low HDL-cholesterolemia, with adjustments for age, gender, smoking, alcohol intake, BMI, hypertriglyceridemia, and genotype. The GG genotype was detected as being a significant associated factor (odds ratio = 0.11 [95% confidence interval = 0.01-0.90], p = 0.01), in addition to BMI and the presence of hypertriglyceridemia. Conclusions. These results suggest that the GG genotype may be an independent protec tive factor associated with low HDL-cholesterolemia in this population, although the role of the UCP-1 A-3826G polymorphism in HDL-C is complex and remains controversial. This hypothesis needs further investigation. (C) 2008 IMSS. Published by Elsevier Inc.