Investigations on the genetic polymorphism in the region ofCYP17gene encoding 5′-UTR in patients with polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder, which is the most common cause of anovulatory infertility and hirsutism. It is caused by an overproduction of androgens in theca cells. In the ovary, androgen synthesis is regulated by 17 alpha-hydroxylase/17,20-lyase enzyme complex containing P450c17 (CYP17). In some individuals, the promoter region of CYP17 gene contains a T-->C substitution that creates an Sp1 site at position-34. This polymorphism generates a recognition site for the MspA1 restriction enzyme. The objective of the study was to investigate the frequency of T-->C substitution of CYP17 gene promoter in women with PCOS and elucidate its role in the pathogenesis of the syndrome. Another aim of the study was to compare the results with the levels of the hormones luteinizing hormone, follicle-stimulating hormone, testosterone and estradiol. The present investigation involved a group of 55 women with PCOS and 56 healthy women without symptoms of PCOS. Following digestion with restriction enzyme MspA1, it was demonstrated that the polymorphic A2 allele is no more frequent in women with PCOS than in healthy women. In the PCOS group, the hormonal profiles were not significantly different in the carriers of a normal allele A1A1 from the carriers of A1A2 and A2A2 alleles. It is concluded that T-->C polymorphism of CYP17 gene is not associated with steroid hormone synthesis in PCOS and is not the primary genetic defect in this disease.

Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

“…In Chinese women, a polymorphism in the promoter region of the aldosterone synthetase gene ( CYP11B2 ), which affects the balance of the ovarian renin–angiotensin system, has been linked to PCOS susceptibility (Zhao et al ., 2003). A polymorphism in the gene for 17α-hydroxylase ( CYP17A1) , which is active in estrogen biosynthesis, was not associated with PCOS susceptibility (Techatraisak et al ., 1997; Diamanti-Kandarakis et al ., 1999; Marszalek et al ., 2001). The CYP19A1 gene encodes a key component of aromatase, which catalyses the production of estrogens from androgens.…”

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

“…In 1994, Carey et al showed significant association of this polymorphism with PCO and male pattern baldness in a family-based study [ 72 ]; however, these findings were not persistent when they increased the sample size [ 73 ]. On similar lines, this polymorphism was not found to be a significant factor for PCOS development in British [ 74 ], Slovenian [ 75 ], Polish [ 76 ], American [ 77 , 78 ], Korean [ 79 ], Chilean [ 80 ], Chinese [ 81 ], Thai [ 82 ], and Indian [ 83 ] women with PCOS or even in Turkish adolescents [ 84 ]. In contrast, Indian women with PCOS showed significantly increased frequency of C allele [ 53 ].…”

CYP17 T/C (rs74357) gene polymorphism contributes to polycystic ovary syndrome susceptibility: evidence from a meta-analysis

“…After screening the full text of these publications, 10 articles were excluded for not meeting the inclusion criteria. Ultimately, 19 eligible case–control studies ( 23 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ) were included in this review in Fig. 1 .…”

“…This finding is analogous with the study done by Park ( 38 ) showing higher expression in the recessive model of CYP17 genotype among PCOS compared with control subjects in a Korean population. However, null associations were observed in Caucasians by Marszalek ( 37 ), Echiburú ( 27 ) and Ushasi Banerjee ( 28 ). Consequently, whether the significant relationship existed in Caucasian women could not be assessed owing to the small number of women in this category, which remains unknown and needs further examination.…”