Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study

Abstract

Objective: Susceptibility of fat mass and obesity-associated (FTO) gene polymorphisms to obesity has been reported in various populations. Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus. However, prognostic significance of these genetic variations has not been fully elucidated. Here, we investigated the involvement of FTO rs9939609 and MC4R rs17782313 polymorphisms in the development of obesity. Association with type 2 diabetes mellitus (T2DM) was also investigated. Subjects: We analyzed 2806 community-dwelling middle-aged to elderly subjects (61±14 years). Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. Results: FTO genotype was significantly associated with current body mass index (BMI; TT 23.2±3.2, TA 23.7±3.2, AA 24.4 ± 3.2 kg m À2 , P ¼ 2.5 Â 10 À6 ) and frequency of obesity (26.6, 32.0, 43.0% respectively, P ¼ 2.0 Â 10 À4 ). Age-and sexadjusted odds ratio for obesity was 1.30 (P ¼ 0.004) in TA and 2.07 (P ¼ 0.002) in AA genotype. During the 9.4 years comprising the follow-up period, 214 new cases of obesity were diagnosed among 1718 subjects whose retrospective data were available. A allele frequency of the FTO genotype was significantly higher in subjects who developed obesity (22.2, 15.8%, P ¼ 0.001), Age-, sex-and initial BMI-adjusted odds ratio for the development of obesity was 1.46 (95% confidence interval, 1.04-2.04) (P ¼ 0.031). However, association studies and meta-analysis of T2DM did not actively support the involvement of FTO genotype. No significant differences were observed between the MC4R genotype and BMI (P ¼ 0.015), and the frequency of obesity (P ¼ 0.284). Conclusion: FTO genotype is an independent risk factor for future development of obesity.

Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals

“…In addition, one article was excluded as it was a review and nine articles were excluded because they investigated the association between the MC4R polymorphism and obesity, obesity-related traits, stroke or polycystic ovary syndrome. Therefore, 13 articles met the primary inclusion criteria, of which one article was excluded because it was a duplicated publication [19] and another article was excluded because it did not provide sufficient data for calculation of an OR with 95% CI [20]. In addition, the nine studies included in the paper by Loos et al [3] were considered as separate studies in the following data analysis.…”

Association of Four Genetic Loci with Uric Acid Levels and Reduced Renal Function: The J-SHIPP Suita Study

“…The personal health records evaluated at previous medical checkups were obtained from a clinical database administrated by the local city council [12]. For each subject, the oldest data available from 1992 to 1996 were obtained.…”

Developments in Obesity Genetics in the Era of Genome-Wide Association Studies

“…In general, studies in populations of East Asian [48,49,50,51,52,53,54,55,56,57,58,59,60,61,62], South Asian [63,64,65] and African origin [66,67,68,69,70,71,72,73], in particular those with larger sample sizes, have found that the FTO locus associates convincingly with BMI and obesity risk, with effect sizes similar to those observed in white European populations. The risk allele frequency of the FTO locus, however, varies substantially: being ∼20% in East Asian populations, ∼30% in South Asians but ∼45% in white Europeans.…”

“…Although the risk allele frequency (∼16–20%) in populations of African ancestry was lower, the effect sizes tended to be similar or even somewhat larger than in white Europeans. Studies of populations of East Asian descent, where the risk allele is less frequent (∼19%) than in white Europeans, have not yet found consistent replication of this locus [52,56,58,60,61,76,77]. A meta-analysis of all available data will be needed to confirm or refute association of this locus with obesity susceptibility in these populations.…”