Short Communication Elmer ress J Clin Med Res • 2011;3(6):319-324 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 Kazuhiko Kotania, b, d, Shinji Fujiwaraa, Kokoro Tsuzakia, Yoshiko Sanoa, Narumi Nagaic, Toshiyuki Yamadab, Naoki Sakanea Abstract 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) choles- terol 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/m2, 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 geno- type (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regres- sion 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 Manuscript accepted for publication October 31, 2011 aDivision of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan bDepartment of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-Tochigi, Japan cDepartment of Food Science and Nutrition, University of Hyogo, Hyogo, Japan dCorresponding author: Kazuhiko Kotani, MD, PhD, Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1 - 1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, 612-8555, Japan. Email: kazukotani@jichi.ac.jp doi:10.4021/jocmr738w 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-sig- niﬁcant 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-choles- terolemia, 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 Introduction Obesity is a global health problem due to its epidemic pro- portions and the detrimental consequences associated with obesity [1, 2]. Uncoupling protein 1 (UCP1) is a mitochon- drial component and a proton transporter, which uncouples oxidative metabolism from ATP synthesis, and dissipates en- ergy through heat production [3, 4]. UCP1 plays important roles in energy homeostasis, and UCP1 gene polymorphisms have been implicated in the pathogenesis of obesity and re- lated metabolic disorders, including lipid disorders [3, 4]. An A-3826G polymorphism within the promoter region of the UCP-1 gene is a candidate gene polymorphic site related to these disorders [5]. The blood levels of high-density lipoprotein (HDL) cholesterol (HDL-C) are a major atherosclerotic risk marker [6, 7]. The HDL-C concentrations are generally determined by the interplay of environmental and genetic factors [7]. Few human studies have directly focused on the relationship between the UCP-1 gene A-3826G polymorphism and HDL-C levels, but inconsistent data on this relationship have been reported in several cross-sectional association studies [8-15]. Although carrying the G allele or G/G genotype was reportedly associated with lower HDL-C levels [9, 11, 13], we found no association between the A-3826G polymorphism and HDL-C levels [8, 10, 12, Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org 319