Polymorphic Variations in VDR Gene in Saudi Women with and Without Polycystic Ovary Syndrome (PCOS) and Significant Influence of Seven Polymorphic Sites on Anthropometric And Hormonal Parameters

Abstract

SummaryBackgroundThis study was designed to evaluate the associations between vitamin D receptor (VDR) gene polymorphisms and biochemical characteristics of Saudi women with polycystic ovary syndrome (PCOS).MethodsSerum levels of LH, FSH, and Vitamin D were measured in 33 women: 16 patients and 17 normal controls (18 to 36 years). DNA was extracted and used for sequencing of the exons of VDR gene using ABI PRISM 3730xi Genetic Analyzer.ResultsWeight, BMI, Vit D, LH and FSH levels were higher in the PCOS patients compared to control group, where Vit D level correlated positively and significantly with FSH, in the control, but showed a negative and non-significant correlation in the PCOS patients. Sequencing results showed extensive polymorphisms in both groups, but the differences in the frequencies were not significant. Demographic and hormonal parameters were compared in the different genotypes of the SNPs. Significant differences were ob served in the values of the studied parameters in rs11168276, rs11168266, rs3858733, rs121909790, rs11168265 and rs731236. Vitamin D level was influenced significantly by the genotypes of rs11168265 (AA) (p=0.008), rs11168276 (AA; p=0.018) and rs731236 (CC; p=0.024).ConclusionVitamin D deficiency does not associate with PCOS in Saudi females. Several SNPs are identified in the VDR gene, in normal and PCOS females, but there is no difference in their frequencies between the two groups. The results show that polymorphism in VDR gene influences certain anthropometric and hormonal parameters in PCOS patients. Further detailed studies are required to confirm the associations between VDR and PCOS.

Decreased serum level of gamma-amino butyric acid in Egyptian infertile females with polycystic ovary syndrome is correlated with dyslipidemia, total testosterone and 25(OH) vitamin D levels

“…(5, 6). Moreover, PCOS is highly combined with insulin resistance (IR) (7, 8), dyslipidemia (6, 9) and obesity (10). Heterogenic factors further contribute to PCOS manifestations (11).…”

Low Vitamin D Level in Saudi Women With Polycystic Ovary Syndrome

“…It is not consistent with that of a study of women with PCOS living in Makkah, located in the Western region, in which the vitamin D levels were similar among patients and controls (25); nonetheless, a larger study in the same region demonstrated lower levels of vitamin D in women with PCOS (17). Of interest is one report in which levels of vitamin D were higher in women with PCOS than in controls; however, the sample size was very small (16 cases and 17 controls), and approximately all participants had a vitamin D level higher than 30 ng/mL [75 nmol/L; (28)].…”

Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review

“…A small study found that the PCOS group had higher vit D and LH levels, while a significant positive correlation was seen be-tween vit D and FSH in control group only. Interestingly, TaqI "CC" genotype was associated with vit D level in PCOS group, but not with LH level [21]. Another study carried on Caucasian women found significantly higher values of hirsutism score, cholesterol, triglycerides, fasting blood glucose and insulin, higher LH and androgens levels, alongside with lower sex hormone binding globulin, FSH and vit D values in PCOS group.…”

“…▶Table 1 Summary data on association between VDR gene polymorphisms and PCOS metabolic/endocrine abnormalities. Fokl Apal Cdx2 TaqI ▪ FokI "TT": increased risk for infertility, acne, alopecia, elevated cholesterol levels ▪ ApaI "AA": higher testosterone levels ▪ TaqI "TC": higher levels of FSH, LH, cholesterol ▪ TaqI "CC": higher testosterone ▪ Cdx2 "GG": traits like acne, hirsutism, AN, increased cholesterol levels ▪ Cdx2 "AA": higher testosterone levels; risk for infertility All in all, studies suggest that higher values of androgen hormones are correlated with TaqI "CC" variant in both Caucasian and Asian population [20,27], the same genotype being also associated with vit D levels [20,21,26].…”

“…It is formed by two promoter regions, eight protein coding exons (2-9) and six untranslated exons (1a-1 f) [20]. The gene is highly polymorphic and many allelic variants due to single nucleotide polymorphisms have been reported, which are variable among different ethnic groups [20,21].…”