Kotani et al 4 subjects, 9%, G/G: 10 subjects, 37%; F = 0.461, P = 0.01) were observed in the obese group. There were signiﬁcant differences in HDL-C levels between the A/G genotype and G/G genotype carriers (P = 0.03) and the prevalence of low HDL-cholesterolemia between the A/G genotype and G/G genotype carriers (P = 0.01) in this group. The other measured factors did not show any signiﬁcant differences between the respective genotype carriers in the non-obese and obese groups (data not shown). The clinical characteristics of the two groups by geno- type (the A/A + A/G genotype group versus the G/G geno- type group) are listed in each group of non-obese and obese subjects in Table 1. In the obese group, the G/G genotype carriers had signiﬁcantly lower HDL-C levels and a signiﬁ- cantly higher prevalence of low HDL-cholesterolemia than the A/A + A/G genotype carriers. The other measured fac- tors did not show any signiﬁcant differences between the two groups by genotype in the non-obese and obese groups. Subsequently, the results of the multivariate-adjusted logistic regression analysis of the presence of low HDL- cholesterolemia are shown in Table 2. In the obese group, the analysis revealed that carrying the G/G genotype, as well as the BMI and TG, was an independent and signiﬁcant posi- tive factor associated with low HDL-cholesterolemia, while the SBP and T-chol showed an independent and signiﬁcant inverse association with low HDL-cholesterolemia. In the non-obese group, the same analysis revealed that the TG showed an independent and signiﬁcant positive association and the T-chol showed an independent and signiﬁcant in- verse association with low HDL-cholesterolemia, while car- rying the G/G genotype exhibited a non-signiﬁcant but re- duced (by one-half) odds ratio (OR) for the association with the presence of low HDL-cholesterolemia. Discussion The present study showed that the G/G genotype of the UCP-1 gene A-3826G polymorphism was an independent and signiﬁcant factor positively associated with low HDL-cholesterolemia in the obese group, while the G/G genotype was a relatively protective factor associated with low HDL-cholesterolemia in the non-obese group. Even though the results of the OR for the G/G genotype on low HDL-cholesterolemia in the non-obese group did not reach a statistically signiﬁcant level, the impact of the reduction of the OR (by one-half) with regard to low HDL- cholesterolemia should not be ignored. The results of the obese group are similar with the previous studies [9, 11, 13], and the results of the non-obese group likely conﬁrm the earlier study [15]. Blood levels of HDL-C are a major atherosclerotic risk marker, and the association between HDL-C metabolism and genetic factors remains to be explored. It is therefore important to note that there may J Clin Med Res • 2011;3(6):319-324 be an opposite trend for the association between the UCP-1 gene A-3826G polymorphism and low HDL-cholesterolemia based on the obesity status of subjects. This may provide a possible explanation for the inconsistent data shown for this association in the previous studies [8-15] and it may also provide further understanding of the different roles of the UCP-1 gene A-3826G polymorphism under obese and non- obese conditions. The precise mechanisms underlying the present ﬁndings are unclear. UCP-1 is a mitochondrial protein, potentially associated with energy homeostasis [3, 4]. UCP-1 is basi- cally expressed in brown adipose tissue, and recent studies have shown that adult humans possess metabolically active brown adipose tissue [18-20]. Changes in the oxidation of free fatty acids in the mitochondria can alter the blood lev- els of lipids through tissue cholesterol transport; thus, this pathway to control blood lipids may be affected by genetic polymorphisms such as the UCP-1 gene A-3826G polymor- phism [13]. The UCP-1 expression is regulated by the extent of obesity, and the G allele has been reported to be relat- ed to a reduction of the expression of the gene in an obese population [9]. This may be one reason for the present ﬁnd- ing that the G/G genotype is positively associated with low HDL-cholesterolemia in obese subjects. On the other hand, the UCP-1 expression remains to be incompletely examined in non-obese populations including lean subjects [9]. There may be a difference in the UCP-1 expression and the role of the A-3826G polymorphism in regulating the levels of blood lipids between obese and non-obese subject-populations. Such a difference may partially account for the present study ﬁndings. In the present study, the TG (in the non-obese and obese groups) and BMI (in the obese group) were factors that were positively associated with low HDL-cholesterolemia. These associations have been well-recognized [21]. In addition, that the T-chol (in the non-obese and obese groups) was a factor inversely associated with low HDL-cholesterolemia is plausible, because HDL-C participates in regulating the T-chol levels. Although the SBP (in the obese group) was a factor that was inversely associated with low HDL-cho- lesterolemia, this appeared to be paradoxical, because low HDL-cholesterolemia is an atherosclerotic risk factor. The reason for this relationship was not determined, so further studies, including the SBP-related confounders, will be re- quired. The present study had a few limitations. The sample size was relatively small, and there was not a very high preva- lence of low HDL-cholesterolemia. This might have lead to the non-signiﬁcance of the association between the G/G genotype and low-HDL-cholesterolemia in the non-obese group. The cross-sectional design of the study did not fully allow for determination of the cause-and-effect relationship between factors. Moreover, although there have been some reports showing the association between HDL-C levels and 322 Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press™ | www.jocmr.org