Kotani Kazuhiko, Sakane Naoki, Saiga Kyoko, Adachi Seiji, Shimohiro Hisashi, Mu Haosheng, Kurozawa Youichi
Division of Health Administration and Promotion, Faculty of Medicine, Tottori University, Yonago, Japan.
Arch Med Res. 2008 Jan;39(1):142-6. doi: 10.1016/j.arcmed.2007.07.002. Epub 2007 Oct 15.
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.
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.
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=0.015). 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.
These results suggest that the GG genotype may be an independent protective 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.
解偶联蛋白-1（UCP-1）基因启动子区域的A-3826G多态性可能参与肥胖和代谢紊乱的病理生理过程。然而，UCP-1 A-3826G多态性对高密度脂蛋白胆固醇（HDL-C）（动脉粥样硬化疾病的主要促成因素）的影响仍未明确。
共有298名健康日本受试者（144名男性和154名女性，平均年龄：45.2岁），体重指数（BMI）为20.0 - 30.0 kg/m²，生活方式规律且未接受药物治疗，纳入这项横断面研究，通过基因组PCR和Bcl1限制性片段长度多态性分析评估血清HDL-C水平与UCP-1 A-3826G多态性之间的关系。我们将日本男性HDL-C的1.04 mmol/L和日本女性的1.29 mmol/L作为低HDL-胆固醇血症的临界值。
UCP-1 A-3826G多态性的基因型和等位基因频率与日本人群先前报道的相似。在男性中，GG基因型的HDL-C水平（1.75±0.49 mmol/L）显著高于AA基因型（1.45±0.34 mmol/L，p = 0.015）。在女性中，低HDL-胆固醇血症的发生率因基因型存在显著差异：GG基因型的患病率较低（AA基因型为15.4%，AG基因型为4.8%，GG基因型为15.4%，p = 0.022）。采用逻辑回归分析确定低HDL-胆固醇血症的危险因素，并对年龄、性别、吸烟、饮酒、BMI、高甘油三酯血症和基因型进行校正。除BMI和高甘油三酯血症外，GG基因型被检测为显著相关因素（比值比 = 0.11 [95%置信区间 = 0.01 - 0.90]，p = 0.01）。
这些结果表明，尽管UCP-1 A-3826G多态性在HDL-C中的作用复杂且仍存在争议，但在该人群中GG基因型可能是与低HDL-胆固醇血症相关的独立保护因素。这一假设需要进一步研究。
