Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans

Abstract

To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m2 heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m2 and 0.9 kg/m2, respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m2, P = 1.17 x 10−10). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m2 (P = 1.15 x 10−5). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development.

Association of <b><i>FTO</i></b> rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

“…It is reported that multiple neighboring single-nucleotide polymorphisms within the first intronic region of the FTO gene are associated with BMI [21]. This is consistent with recent findings showing that different variants within the FTO gene are associated with different classes of obesity [6]. Moreover, a study by Sentinelli et al [20] showed an association between the common FTO rs9939609 polymorphism with BMI in an Italian population; however, a stronger association was observed with another polymorphism, rs9930506, within the FTO gene suggesting the impact of other polymorphisms on BMI.…”

“…It had been reported that the common variant rs9939609, found in the first intron of the FTO gene, is one of the most commonly replicated polymorphisms associated with obesity in both children and adults [4]. Although the association has been reported in all age groups and in both genders, inconsistency exists with studies supporting the association as being age- and gender-dependent [5, 6]. The association between FTO variants and BMI has also been reported to interact with both physical activity [7] and dietary intake [8], with physical activity attenuating the impact of FTO on BMI.…”

“…The association between FTO variants and BMI has also been reported to interact with both physical activity [7] and dietary intake [8], with physical activity attenuating the impact of FTO on BMI. FTO variants have also been reported to be associated with obesity in different ethnic backgrounds [5, 6]. Hence, the association between FTO and obesity could be influenced by multiple factors.…”

Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

“…[9]. Several studies have further assessed the sex-dependent effects [10-13]. Moreover, novel sexual-dimorphic genetic loci have been identified via sex-stratified GWAS [7, 14, 15].…”

Gene-environment interactions as the basis of health formation

“…В отношении ассоциаций вариантов гена FTO значи-мой оказалась половая принадлежность индивидов: для некоторых полиморфных вариантов у мужчин зареги-стрирована доминантная модель предрасположенности к ожирению, тогда как у женщин по этим же вариантам реализовывалась аддитивная или рецессивная модель предрасположенности [51]. Для мужчин и женщин с од-ними и теми же генотипами по rs9939609 гена FTO пока-зана разнонаправленная динамика изменения риска раз-вития ожирение в зависимости от числа выкуриваемых сигарет [32].…”