The Association Between the Uncoupling Protein-1 Gene A-3826G Polymorphism and High-density Lipoprotein Cholesterol in A General Japanese Population: A Consideration of the Obesity Status

BACKGROUND: Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. METHODS: Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2), and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. CONCLUSIONS: The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk