Genetic Determinants of Premature Menopause in A Mashhad Population Cohort

Mirinezhad, Mohammad Reza; Khosroabadi, Narges; Rahpeyma, Maliheh; Khayami, Reza; Hashemi, Reza; Ghazizadeh, Hamideh; Ferns, Gordon A; Pasdar, Alireza; Ghayour‐Mobarhan, Majid; Hamzehloei, Tayebeh

doi:10.22074/ijfs.2020.134688

Genetic Determinants of Premature Menopause in A Mashhad Population Cohort

Document Type : Original Article

Authors

¹ Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

² Department of Genetics, Faculty of Biological science, Shahid Beheshti University,Tehran, Iran

³ Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

⁴ Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

⁵ International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran

⁶ Brighton and Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK

⁷ Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

10.22074/ijfs.2020.134688

Abstract

Background: Premature menopause is characterized by amenorrhea before age of 40 years, markedly raised serum
luteinizing hormone (LH) level, follicle-stimulating hormone (FSH) level and reduced serum level of estradiol.
Genome-wide analysis suggested several loci associated with premature menopause. Here, we aimed to analyze association
of variants at the MCM8, FNDC4, PRRC2A, TLK1, ZNF346 and TMEM150B gene loci with premature
menopause.

Materials and Methods: In this cross-sectional study, a total of 117 women with premature menopause were compared
to 183 healthy women. Anthropometric indices were measured in all participants: height, weight, body mass index
(BMI), waist circumference (WC) and wrist circumference. Eight single-nucleotide polymorphisms (SNPs) of the
indicated genes (rs16991615, rs244715, rs451417, rs1046089, rs7246479, rs4806660, rs10183486 and rs2303369)
were identified from the literature. Genotyping was performed using tetra-ARMS polymerase chain reaction (PCR)
and ASO-PCR methods.

Results: T allele of the rs16991615, rs1046089, rs7246479 and rs10183486, C allele of rs244715, rs451417 and
rs4806660 as well as TT genotype of rs2303369 were associated with an increased risk of premature menopause,
likely causing susceptibility to primary ovarian insufficiency (POI) in comparison with C allele. We also found an
association between the rs16991615 SNP with premature menopause. Frequency of the minor allele in cases was
increased for all SNPs in comparison with controls. All minor alleles, except for rs2303369, showed a statistically
significant increased odds ratio (OR). However, after Bonferroni correction for multiple testing, none of the P values
were remained significant.

Conclusion: The selected polymorphisms in MCM8, FNDC4, PRRC2A, TLK1, ZNF346 and TMEM150B genes
may potentially affect susceptibility to premature menopause, although replication of the results in larger cohort could
clarify this.

Keywords

20.1001.1.2008076.2021.15.1.5.9

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