Association between Genetic Variants Linked to Premature Ovarian Insufficiency and Inflammatory Markers: A Cross-Sectional Study

Abstract

Background: Premature menopause (PM) is the cessation of ovarian function before age 40. PM women are more likelyto have cardiovascular diseases (CVDs), diabetes, and mental disorders. This is the first study that assessed the associationof single nucleotide polymorphisms (SNPs) with anti-heat shock protein 27 (Hsp27), High-sensitivity C-reactive protein(hs-CRP), and PM and serum pro-oxidant-antioxidant balance (PAB), as putative risk factors for CVDs. We aimed toexplore the association of oxidative stress markers with eight different SNPs shown to be related to premature menopause.Materials and Methods: In this cross-sectional research, we included 183 healthy women and 117 premature menopausalwomen. We determined baseline characteristics for all participants and measured serum hs-CRP, anti-HSP-27 antibody titer, and PAB levels using the established methods. Genotyping for eight SNPs was done usingthe tetra amplification refractory mutation system polymerase chain reaction (Tetra-ARMS PCR) and allele-specificoligonucleotide PCR (ASO-PCR) methods.Results: We found a significant difference between mean serum PAB levels and the genetic variant of rs16991615(P=0.03). ANCOVA showed a significant effect of the genotypes rs4806660 and rs10183486 on hs-CRP serum levelsin the case and control groups, respectively (P=0.04 and P=0.007). ANCOVA also showed an association betweenrs244715 genotypes and anti-hsp27 serum levels in the case group (P=0.02). There was a significant effect of thegenotypes of rs451417 on the serum hs-CRP level in the control group (P=0.03).Conclusion: There was a significant association of the genetic variants related to PM with oxidative stress and inflammatorymarkers (serum PAB, anti-hsp27 antibody, and hs-CRP). Accordingly, this seems to be an effective approach topredicting susceptible subjects for cardiovascular and mental disorders as well as various cancers.

Keywords

• genetic variant
• hs-crp
• inflammatory marker
• premature ovarian insufficiency