Single nucleotide polymorphisms inRenalaseandKCNQ1genes and female infertility: A cross‐sectional study in Pakistan

Abstract

A global increase in the incidence of subfertility is observed, and research suggests strong genetic influences that might restrict fertility directly or indirectly. It therefore becomes important to rule out the existence of genetic causes and counsel infertile couples before offering “Advanced Infertility Treatment Techniques.” This cross‐sectional study aimed to explore the association of KCNQ1 (rs2237895) and Renalase (rs2576178 and rs10887800) single nucleotide polymorphisms with different causes of infertility by analysing 508 fertile and 164 infertile women. Gene variant (AC/CC) of KCNQ1 rs2237895 showed a slight difference in the endometriosis group compared to the fertile group (p = .049), with the C allele showing a significant association with infertility overall (OR = 1.42 [1.100–1.833]; p < .0069). The variant AG/GG of Renalase rs2576178 was significantly associated with overall infertility (OR = 2.266; p < .001), with a strong G allele association with unexplained infertility OR = 2.796 (p = .002) that remained significant after adjusting for age and body mass index. Similarly, Renalase rs10887800 AG/GG and G allele showed significant association with both infertility due to polycystic ovarian syndrome and unexplained infertility. Expression of single nucleotide polymorphism rs2237895 and rs2576178 in both KCNQ1 and Renalase genes might be responsible for altering reproductive potential, hence leading to infertility in women.

Renalase—A new understanding of its enzymatic and non‐enzymatic activity and its implications for future research

“…Among all potentially applicable records only 43 focused on the subject by title and abstract. These papers were screened and divided into three areas: renalase enzymatic activity (16 records), 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 renalase polymorphisms (16 records) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and renalase non-enzymatic activity (11 records). [34][35][36][37][38][39][40][41][42][43][44]…”

“…Interestingly, both rs2576178 and rs10887800 were suggested to be involved in the pathogenesis of coronary artery disease (CAD). 27,28 Hu et al 27 carried out a case-control study that included a total of 449 CAD patients and 507 healthy controls. Their results revealed that renalase rs2576178 GG (homozygous mutant) was significantly associated with increased risk of CAD (GG compared with AA -wild type, OR = 1.60, 95% CI = 1.07-2.39, P = .022).…”

“…In this study, the rs2576178 polymorphism did not influence the risk of CAD. 28 Such erratic research results highlight the need to carry out studies with similar study designs, unified and vast selection of study groups, as well as unified diagnostic criteria of CAD that often differ between studies. Aforementioned Polish case-control study also included SNP rs10887800 and showed that GG genotype was associated with an increased risk of CAD under the codominant model and under the recessive model.…”

“…Aforementioned Polish case-control study also included SNP rs10887800 and showed that GG genotype was associated with an increased risk of CAD under the codominant model and under the recessive model. 28 However, reliable conclusions cannot be drawn without more data.…”

Associations between renalase concentration and the occurrence of selected diseases

“…The study proved a significant correlation of SNPs rs2576178 and rs10887800 with female infertility of unknown cause and with infertility caused by polycystic ovarian syndrome. Scientists have hypothesised that SNPs in the renalase gene may interfere with the hormonal hypothalamic-pituitary-associated ovarian axis by affecting the degradation of catecholamines and increasing the number of stress hormones [47]. The link between renalase and the reproductive system is supported by the fact that Zhou et al proved that the gonads and adrenal cortex are a source of renalase and suggested that it may affect fertility [3].…”