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=0.015). 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.


CONCLUSIONS
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.
Kotani
Kazuhiko
K
Division of Health Administration and Promotion, Faculty of Medicine, Tottori University, Yonago, Japan. kakotani@grape.med.tottori-u.ac.jp
Sakane
Naoki
N
Saiga
Kyoko
K
Adachi
Seiji
S
Shimohiro
Hisashi
H
Mu
Haosheng
H
Kurozawa
Youichi
Y
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071256:Uncoupling Protein 1
D008076:Cholesterol, HDL; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1