The HIF2α polymorphism rs4953361 is associated with impaired glucose metabolism in Han Chinese women with infertility

Abstract

Objective: To evaluate HIF2α polymorphisms and glucose metabolism in a group of women with and without infertility. Design: Case–control study.Setting: Female infertility patients who visited this reproductive center and age-matched females without infertility who underwent routine health examinations from January 2020 to December 2021.Patients: The study group consisted of 148 women with infertility and 176 women without infertility as healthy controls.Intervention: We genotyped 29 single nucleotide polymorphisms (SNPs) of HIF2α by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping technology. The genetic associations were analyzed statistically.Main Outcome Measures: Allele frequency, genotype distribution and haplotype analysis of the HIF2α polymorphisms. BMI, glucose metabolism and insulin release were also measured. Results: Infertile women had elevated BMI, impaired glucose metabolism, and increased levels of plasma insulin compared to those of healthy women. SNP analysis of HIF2α revealed that the allele and genotype frequencies of rs4953361 were significantly associated with female infertility. Haplotype analysis of HIF2α polymorphism identified haplotypes TGG and TGA as being associated with female infertility. Women with the AA genotype of rs4953361 had a significantly higher BMI and postload plasma glucose and insulin levels than those of women with the GG genotype.Conclusion: This is the first study to report an association between HIF2α polymorphisms and female infertility and glucose and insulin metabolic disorder. These results require replication in larger populations but suggest that the HIF2α polymorphisms may play an important role in female obesity-related infertility. In this observational study, we did not report the results of a health care intervention on human participants. The study was approved by the Human Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. Clinical data and peripheral blood samples were collected only after explaining the objectives of the study and obtaining a signed informed consent form.