rs9939609 FTO genotype associations with FTO methylation level influences body mass and telomere length in an Australian rural population

Yuling Zhou, David Simmons, Donna Lai, Brett D. Hambly, Craig S. McLachlan

Research output: Contribution to journalArticlepeer-review

Abstract

Background: the fat mass- and obesity-associated (FTO) gene influences energy homeostasis in humans. While the obesity-related variant, rs9939609 has been replicated across a number of cohort studies, there remain significant variance and a low modest association. Telomere length is another commonly reported obesity risk factor. We hypothesize understanding the associations between FTO rs9939609 with FTO methylation and telomere length will provide a more accurate assessment of obesity risk. Methods: 942 participants free of diabetes or pre-diabetes were included in the retrospective study. Leukocyte genomic DNA was analyzed for rs9939609 genotyping, FTO gene methylation and LTL measurement. Results: rs9939609 AA genotypes were associated with increased fat percentage (3.15%, P=0.001), fat mass (4.16 kg, P=0.001), body mass index (BMI) (1.38, P=0.006) and waist circumference (3.35 cm, P=0.006), but not with FTO methylation or LTL in this overall population. However, when participants were stratified into higher and lower FTO methylation groups, the AA genotype possesses a 2.04-fold increased obesity risk in comparison to TT genotype (95%CI, 1.07 - 3.89, P=0.031) in participants with a higher FTO methylation level, but this association was absent in the lower FTO methylation sub-group. Moreover, AT and AA genotype carriers were associated with shorter LTL compared to TT carriers (P=0.020 and P=0.111, respectively) in the higher FTO methylation level group. However, this association was absent in the lower methylation group. Furthermore, FTO gene methylation level was significantly associated with LTL in the 942 samples (P=0.017). Conclusions: FTO rs9939609 is associated with obesity risk and LTL in this study, where this association is only observed at higher FTO methylation levels of participants. Our data suggest association of multiple factors, including FTO methylation level, may be involved in one of several mechanisms underlying the commonly reported obesity risk of this FTO polymorphism.
Original languageEnglish
Pages (from-to)1427-1433
Number of pages7
JournalInternational Journal of Obesity
Volume41
Issue number9
DOIs
Publication statusPublished - 2017

Keywords

  • obesity
  • single nucleotide polymorphisms
  • telomere

Fingerprint

Dive into the research topics of 'rs9939609 FTO genotype associations with FTO methylation level influences body mass and telomere length in an Australian rural population'. Together they form a unique fingerprint.

Cite this