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18.97.9.175
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Short leukocyte telomere length is associated with FTO rs9939609 polymorphism in non-obese individuals
( Ji Hee Yu ) , ( Inkyung Baik ) , ( Kyoung Jin Kim ) , ( Su Kang Jeong ) , ( Yun Joo Kim ) , ( Jee-in Heo ) , ( Ji A Seo ) , ( Sin Gon Kim ) , ( Kyung Mook Choi ) , ( Sei Hyun Baik ) , ( Dong Seop Choi ) , ( Chol Shin ) , ( Nan Hee Kim )
UCI I410-ECN-0102-2021-500-000693171
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Objective: The fat mass and obesity-associated (FTO) gene polymorphism rs9939609 has been associated with body weight and adiposity in many studies. Obesity contributes to limited life expectancy and short telomere length, a cellular marker for biological age. Our study aimed to evaluate the association between FTO rs9939609 risk variant and leukocyte telomere length, and to investigate if this relationship is modified by the status of obesity. Methods: A total of 2133 participants were recruited from the Korean Genome and Epidemiology Study. Leukocyte telomere length was determined using real-time quantitative polymerase chain reaction methodology. The FTO rs9939609 polymorphism was genotyped using DNA samples collected at baseline. Results: The proportion of the TT, TA, and AA genotypes were shown as 76.7, 21.5, 1.8%, respectively. The mean body mass index (BMI) was significantly higher in carriers with the A-risk allele than in those with TT genotype (25.1 vs. 24.6 kg/m2, P = 0.002). In 1,184 subjects without obesity (BMI < 25 kg/m2), BMI, waist circumference and visceral fat area were higher in those with the FTO risk allele than in non-carriers. In contrast, none of them were associated with FTO risk allele in those with obesity. Leukocyte telomere length was significantly shorter in carriers with the FTO risk allele compared with non-carriers after controlling for age, sex, BMI, smoking, alcohol, exercise, hypertension, diabetes and cardiovascular disease (P < 0.01). In particular, such significant association between the FTO risk allele and telomere length appeared only in non-obese subjects (P = 0.03). In stepwise multivariate linear regression analyses, the independent risk factors affecting shorter leukocyte telomere length were higher age, lower high-density lipoprotein cholesterol levels and the presence of the FTO risk allele. This finding was evident only in those without obesity. Conclusion: The FTO rs9939609 polymorphism is the independent risk factor not only for obesity but also for biological aging in non-obese population.

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