Interaction between FTO-rs3751812 and physical activity on obesity in Taiwan

• Main Authors: Yi-Ching Liaw, 廖誼青
• Other Authors: Tsuo-Hung Lan
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/8h97tk

碩士 === 國立陽明大學 === 臨床醫學研究所 === 105 === Introduction Obesity is a major public health related issue in the world. To date, fat mass and obesity-associated (FTO) gene is considered as the most significant genetic contributor to the polygenic obesity. However, how the body mass index (BMI)-increasing influence of FTO is attenuated in physically active individuals in Asia is not well understood. Therefore, we investigated the BMI-increasing influence on major single nucleotide polymorphism (SNP) in FTO gene among different physically active individuals. Materials and Methods The study subjects were obtained from the Taiwan Biobank which is a large-scale population-based genetic database. A total of 10853 subjects were recruited. Data from the biobank were analyzed based on demographic information (age, sex), body weight and height (measured in accordance with the standard procedures), lifestyle information (physical activity), total cholesterol, smoking habits (never/former and current smoker), alcohol consumption, vegetarian diets, and coffee and tea consumption. In this study, we chose nine FTO gene SNPs (rs6499640, rs1121980, rs17817449, rs8050136, rs9935401, rs3751812, rs9939609, rs9930506 and rs9922708) to determine their roles on the risk for obesity. In addition, we chose a tag-SNP in the final model. Information on nine SNPs were collected from Taiwan Biobank chip (TWB chip). Linear regression and logistic regression models were used to investigate the relationship between the tag-SNP and each variable (age, sex, physical activity, alcohol drinking, smoking, total cholesterol, tea consumption, coffee consumption, and vegetarian diets) based on BMI. All analyses were conducted using SAS 9.3 statistical software. Hardy–Weinberg equilibrium was tested for each SNP using a one-degree of freedom χ2-test. Linkage disequilibrium (LD) and its correlation coefficients (D` value) were calculated using Haploview software. Results In this study, we found that the eight FTO gene SNPs (rs1121980, rs17817449, rs8050136, rs9935401, rs3751812, rs9939609, rs9930506 and rs9922708) confer a similar magnitude of risk for obesity. The correlations were high among all the eight SNPs in the LD analysis. Finally, we chose the tag-SNP rs3751812 in the final model. After excluding the missing values, a total of 10832 people were analysed. 168 subjects were homozygous for the obesity risk allele (TT) of the FTO tag-SNP rs3751812, 2343 were heterozygous (TG), and 8321 were wild-type (GG). From the linear regression, we found that the addition of T allele was significantly associated with increased BMI (p<0.0001). Individuals with GG genotype who were physically active exhibited lower BMI (β=-0.368, p<0.0001) compared to their physically inactive counterparts. In addition, individuals with TG genotype who were physically active also appeared to exhibit significantly lower BMI (β=-0.414, p=0.0175) compared to the physically inactive group. No significant effect was found with respect to the BMI of people with TT genotype who were physically active compared to those that were physically inactive (β=-1.059, p=0.1099). This may have been due to the small sample size. Despite the non-significant results, it could still be observed that physical activity (PA) was beneficial in lowering the BMI compared to “non-physical activity”. In the non-PA group, the addition of T allele was significantly associated with increased BMI (TT genotype: β=0.950, p=0.0188; TG genotype: β=0.381, p=0.0021). The p-value for linear trend was 0.0002. However, no dose-related trends were observed in the PA group. Results from the logistic regression analysis showed that carriers of one risk allele were significantly associated with a 1.365-fold increased risk of obesity than were those without risk alleles (OR=1.365, 95% CI= 1.208~1.543). Individuals with GG genotype who were physically active exhibited lower obesity risk (OR=0.808, 95% CI: 0.706~0.924) compared to their physically inactive counterparts. Moreover, individuals with TG genotype who were physically active also appeared to exhibit significantly lower obesity risk (OR=0.733, 95% CI: 0.582~0.923) compared to the physically inactive counterparts. No significant effect was found in individuals with TT genotype who were physically active compared to those that were physically inactive (OR=0.452, 95% CI: 0.159~1.282). This may have been due to the small sample size. Despite the non-significant results, it could still be observed that PA was beneficial in lowering the obesity risk compared to “non-PA.” Conclusions Our results strongly suggest that the increased BMI owing to genetic susceptibility by FTO variants (rs3751812, TG) might be blunted through PA.