It has been newly reported in recent studies that single-nucleotide polymorphisms (SNPs) in the first intron of the FTO gene have been associated with BMI in whites. To determine whether the gene is associated with BMI in Asians also, we performed a replication study of the association of the gene with BMI in a Korean population. Two SNPs in the FTO gene (rs1421085 and rs17817449) were genotyped using the TaqMan method in a Korean population (n = 1,733). The two SNPs were then used for an association study with BMI through statistical analyses. The rs1421085 C allele (P = 0.0015, effect size = 0.0056) and rs17817449 G allele (P = 0.0019, effect size = 0.0053) were found to be significantly associated with increased BMI. Our results suggest that FTO may be one of the worldwide obesity-risk genes.Obesity (2008) 16, 2187-2189. doi:10.1038/oby.2008.314 Obesity is one of the most common disorders in clinical practice and is closely related to a number of pathological disorders such as noninsulin-dependent diabetes, hypertension, cancer, gallbladder disease, and atherosclerosis. A large number of genetic association studies suggest that polymorphic variants in genes are associated with BMI (1).Recently, three independent studies have found that common variants in intron 1 of the FTO gene (fat mass and obesity associated; #MIM:610966) were found to be associated with BMI (2-4), and those findings have been replicated in several white populations (3,5,6). However, among other ethnic populations (Asians and Africans), the genetic effects of polymorphisms in intron 1 of FTO have been controversial. The rs9930506 was not associated with obesity-related phenotypes including BMI, weight, and hip circumference in 1,101 African Americans (4). In addition, among oceanic populations (Melanesians, Micronesians, and Polynesians), rs9939609 was not associated with BMI (7). In a Japanese population (864 type 2 diabetes patients and 864 controls), rs8050136 and rs9939690 were not found to be associated with BMI either, although one variant, rs8050136, was associated with the risk of type 2 diabetes (8).A number of highly linked single-nucleotide polymorphisms (SNPs) have been reported to be associated with BMI in previous studies. In this study, in an effort to replicate the association with BMI among Asians, we examined genetic effects in a Korean cohort (n = 1,733) with two SNPs (rs1421085 and rs17817449) that had been reported in white populations (3). To compare the genetic effects directly, we selected the two The genotype distributions of the two SNPs (rs1421085 and rs17817449) in high-BMI individuals (>25 (kg/m 2 )) were in Hardy-Weinberg equilibrium (P = 0.84 and 0.97, respectively). However, genotype distributions among low-BMI individuals (≤25 (kg/m 2 )) were significantly deviated from HardyWeinberg equilibrium (P = 0.011 for rs1421085 and P = 0.011 for rs17817449). Those deviations of FTO variants might be indirect evidence for association of those variants with BMI. The minor allele frequencies of rs1421085 and rs1781...

Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m2) and MC4R variants (effect size ≃ 0.64 kg/m2). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.