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Differential Association of FTO Gene variants and Haplotypes with the Susceptibility to Polycystic Ovary Syndrome According To Obesity in Women with PCOS.

Wassim Y AlmawiRita NemrTomiris AtazhanovaZainab H MalallaSameh SarrayFekria E MustafaNaeema A Mahmood
Published in: Reproductive sciences (Thousand Oaks, Calif.) (2023)
We explored the relation between FTO single gene variants (rs1861868, rs9939973, rs1421085, rs1121980, rs17817449, rs8050136, rs9939609, rs9930506, and rs8044769) and polycystic ovary syndrome (PCOS), in particular, according to the obesity status. This retrospective population-based case-control study involved women with PCOS (583) and 713 eumenorrheic control women; genotyping was done by real-time PCR. Significantly higher minor allele frequency (MAF) of rs9939973, rs17817449, rs9939609, and rs9930506 and lower MAF of rs1121980 were seen in PCOS cases. Lower risk of PCOS was associated with rs1121980 and rs8050136 heterozygous and minor allele-homozygous genotypes, while an elevated risk of PCOS was seen with minor allele-homozygous rs9939973, rs17817449, and r9939609 heterozygous and genotypes and minor allele-homozygous rs9930506 and rs8044769 genotype. While none of the tested FTO SNPs variants was associated with PCOS in normal body weight/lean subjects, rs9939973, rs9939609, and rs9930506 were negatively associated with PCOS in overweight subjects. In comparison, rs1861868 was negatively, while rs8044769 was positively associated with PCOS in obese subjects. Haplotype analysis identified haplotypes GACCTCTAT, AACCTCTAT, AACCTATAT and AGTTGCAGC, and GACCTCTAC to be positively associated with PCOS, while haplotypes GGTTGAAGC, GACCTATAT, GGTTGCAGC, and GATCTATAT were negatively associated with PCOS. Apart from GGTTGAAGC, these haplotypes remained associated with altered risk of PCOS after adjusting for covariates. In addition to rs17817449, rs9939609, rs9930506, and rs1121980, this study is the first to demonstrate association of rs9939973 and rs8044769 with altered risk of PCOS and the first to confirm the BMI dependency on the association of FTO variants with PCOS. This underscores the role of FTO gene variants as predisposing factors of PCOS.
Keyphrases
  • polycystic ovary syndrome
  • insulin resistance
  • type diabetes
  • weight loss
  • body weight
  • skeletal muscle
  • dna methylation
  • physical activity
  • transcription factor
  • high throughput
  • weight gain
  • postmenopausal women