Association of SNP rs.2414096 CYP19 gene with polycystic ovarian syndrome in Iranian women

Abstract

Background: Genetic factors are believed to play an important role in the etiology of polycystic ovarian syndrome (PCOS) which is the most common endocrinological disorder of women in their reproductive age. Androgen metabolism is impaired in PCOS and, thus, CYP19 gene which is involved in this pathway can be a candidate gene. Previous studies have shown a relationship between single nucleotide polymorphism (SNP) of CYP19 in hyperandrogenism and PCOS in some racial groups. Objective: This study was designed to elucidate the role of CYP19 gene in PCOS in Iran. Materials and Methods:In this case-control study, 70 PCOS women and 70 non-PCOS women as normal control were selected. Following the informed consent, 5 ml blood was taken from individuals and subsequently, genomic DNA was extracted by salting out method. Furthermore, a set of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was carried out using specific primers for SNP rs.2414096 followed by enzyme digestion, with HSP92II. Results: Genotype frequencies of SNP rs. 2414096 in PCOS women were as follows: AA (14.4%), AG (44.3%), and GG (41.4%) while in normal group, genotypes were 24.3%, 52.8%, and 22.9%, respectively. Allele frequencies in PCOS group were 49.3% for A and 50.7% for G, whereas normal group had a different percentage of A (36.4%) and G (63.6%). The calculations for both genotypic and allelic frequencies showed statistical significance difference. Conclusion: Variants of SNP rs. 2414096 in CYP19 could play a role in the development of PCOS in Iranian women.

Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women

“…Our results are in accordance with the case–control study carried out by Jia et al, on 684 individuals consisting of 386 PCOS women and 298 controls who reported increased frequency of the mutant homozygous genotype (AA) in non-PCOS women over the PCOS patients suggesting protective nature in Chinese population 13 . Similar to our results, a study by Hemini et al, and Mehdizadeh et al, also found a significant variation in genotypic and allelic frequencies in SNP rs.2414096 of CYP19 between the case and control groups and concluded that this SNP is associated with the pathogenesis of PCOS 15 , 16 . Similar results were observed by Mutib et al, who reported a positive association of rs2414096 polymorphism of CYP19 gene with hyperandrogenism and PCOS in Iraqi women 17 .…”

Polycystic ovarian syndrome: Environmental/occupational, lifestyle factors; an overview

“…Studies also revealed an association between an SNP of the CYP19 gene in hyperandrogenism and PCOS in some ethnic groups. The studies further stated that among Iranian women, variants of SNP rs.2414096 in CYP19 could be responsible for the occurrence of PCOS (40). All these studies clearly suggest the role of genetic factors in the appearance of PCOS.…”

“…The genetic risk calculated by GWAS studies was significantly connected with PCOS and associated clinical features (39). There is a report that indicated that androgen metabolism was deteriorated in women with PCOS, thus the CYP19 gene, which is associated in this pathway, can be a novel gene for investigation (40). Studies also revealed an association between an SNP of the CYP19 gene in hyperandrogenism and PCOS in some ethnic groups.…”

Molecular and Structural Evolution of Cytochrome P450 Aromatase

“…Interestingly, this consensus sequence includes R264 in human aromatase that is mutated into a Cys or His in some polymorphisms that are also reported to alter aromatase activity when used in combination with polymorphic variants of CPR [ 66 ]. Moreover, they have been associated with an increased risk for estrogen-dependent pathologies such as breast cancer and polycystic ovary syndrome [ 67 , 68 , 69 , 70 ].…”