Dataset Information

Family history of menstrual irregularity or diabetes mellitus enhances the susceptibility to polycystic ovary syndrome among subjects harboring rs7903146 genetic variant of TCF7L2.

ABSTRACT:

Purpose

TCF7L2 mediated Wnt signaling cascade regulates glucose homeostasis by orchestrating expression, processing, and hepatic clearance of insulin. Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) significantly overlap in pathophysiological features with insulin resistance as a central driver. While TCF7L2 is the most potent T2DM locus, studies on the association of TCF7L2 with PCOS are limited and inconclusive. Therefore, in addition to expression profiling, the association of TCF7L2 polymorphic variant rs7903146 with PCOS was evaluated.

Methods

Using Rotterdam-2003 criteria for the diagnosis, 120 PCOS cases, and 120 age-matched controls were recruited. Subjects underwent clinical, biochemical, and hormonal assessment, followed by genotyping for rs7903146, carried out by PCR-RFLP and TCFL2 expression profiling by qRT-PCR. Genotype-phenotype correlation analysis was performed to evaluate any such associations. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed by conditional logistic regression.

Results

Higher odds of developing PCOS were observed in the women having a family history (FH) of either T2DM (OR = 3.86, 95% CI:1.90 - 7.83), hirsutism (OR = 4.74. 95%CI: 1.91 - 17.21) or menstrual irregularities (MI) (OR = 3.07, 95%CI: 1.61 - 8.54). The genotypes of rs7903146 did not confer any risk for developing PCOS (OR = 0.46;95%CI: 0.15 - 2.03). However, the elevated risk was seen in the subjects who harbored the variant allele and had FH of either T2DM (OR = 6.71; 95%CI: 1.89 - 23.78) or MI (OR = 9.71; 95% CI:1.89 - 23.78).

Conclusion

TCF7L2 polymorphic variant rs7903146 is not independently linked to PCOS risk, but modulates the risk in the subjects having a family history of either T2DM or MI.

Supplementary information

The online version contains supplementary material available at 10.1007/s40200-022-01050-y.

SUBMITTER: Rashid R

PROVIDER: S-EPMC9167401 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Family history of menstrual irregularity or diabetes mellitus enhances the susceptibility to polycystic ovary syndrome among subjects harboring rs7903146 genetic variant of <i>TCF7L2</i>.

Rashid Rabiya R Shah Idrees A IA Asrar Mir M MM Godha Meena M Ganai Bashir A BA Ganie Mohd Ashraf MA

Journal of diabetes and metabolic disorders 20220517 1

<h4>Purpose</h4><i>TCF7L2 </i>mediated Wnt signaling cascade regulates glucose homeostasis by orchestrating expression, processing, and hepatic clearance of insulin. Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) significantly overlap in pathophysiological features with insulin resistance as a central driver. While <i>TCF7L2</i> is the most potent T2DM locus, studies on the association of <i>TCF7L2</i> with PCOS are limited and inconclusive. Therefore, in addition to expres ...[more]

PMID: 35673429

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