Genetic Variants miR-126, miR-146a, miR-196a2, and miR-499 in Polycystic Ovary Syndrome.

Introduction: Alterations in certain microRNAs (miRNAs) and their target genes have reported in polycystic ovary syndrome (PCOS) and other disease of the female reproductive system, and so may be potential biomarkers. We hypothesised alterations in the prevalence of four miRNAs single nucleotide polymorphism (SNP) variants miR-126 rs4636297, miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444 in women with PCOS in comparison to healthy controls. Methods: SNPs in the four miRNAs were determined in 385 patients and 385 controls by standard RT-PCR techniques. Results: SNPs in miR-126 and miR-246a were significant linked with PCOS under the allelic, dominant, co-dominant, and recessive models (all p ≤ 0.01). The SNP in miR-499 was linked to PCOS in allelic (T, p = 0.002), dominant (p = 0.035) and recessive (p = 0.003) models. The SNPs -196a was significant linked to PCOS only in the recessive model (p = 0.037). Combining these SNPs in miR-499, mi146a, miR-196a and miR-126 respectively into allele haplotypes found highly significant odds ratios (95% CI) of 0.40 (0.29-0.54) (p < 0.001) for the C-G-C-G haplotype, and 0.46 (0.30-0.70) (p = 0.002) for the C-C-C-A haplotype (p = 0.002) for PCOS. Conclusion: Single SNPs and haplotype combinations in certain SNPs in miR-126, miR-146a, miR-196a2 and miR-499 are strongly linked to PCOS, and so may be useful predictors of this condition.

MicroRNA variants in endometriosis and its severity.

Background: MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development.Method: We evaluated the prevalence of miRNAs variants miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 in endometriosis in 260 cases and 260 controls. DNA was extracted and genotyping of the SNPs was carried out by PCR.Results: There was a significant association of rs2910164 and rs2292832 with increased rates of endometriosis under the dominant (p < 0.001), recessive (p < 0.05), co-dominant (p < 0.001), and allelic model (p < 0.001). Also, rs3746444 showed a borderline association with endometriosis under the recessive model (p = 0.05); however, rs11614913 was not linked to endometriosis. Further analysis indicated the significant association of miR-146a rs2910164 polymorphism genotypes (GG, GC, and CC) and miR-149 rs2292832 genotypes (CC and CT) with endometriosis severity in patients (p < 0.001). Additionally, haplotype frequency in cases compared to controls and Linkage disequilibrium (LD) between the mentioned SNPs was appraised.Conclusion: MiR-146a, miR-149 and miR-499 may have a role in the pathogenesis of endometriosis.

The effects of human immunodeficiency virus, human papillomavirus, herpes simplex virus-1 and -2, human herpesvirus-6 and -8, cytomegalovirus, and hepatitis B and C virus on female fertility and pregnancy.

Female infertility may be defined as a woman of reproductive age being unable to become pregnant after a year of regular unprotected sexual intercourse. Social, genetic, endocrine, physiological, and psychological factors as well as lifestyle habits (i.e., smoking and alcohol consumption), either alone or in combination with male factors, are major causes. However, approximately 15-30% of cases of female infertility remain unexplained. Numerous investigations have also indicated that microbiomes play an important role in human reproduction. All parts of the female reproductive system may be influenced by infectious and pathological agents, especially viruses, and these may interfere with reproductive function and so are risk factors for infertility, although in many cases an exact role is unclear. We present an overview of the impact of common viral infections on female reproduction, searching Medline, PubMed, Scopus, and Google scholar databases for potentially relevant studies of viruses known to have a potential effect. Human immunodeficiency virus (HIV), herpes simplex virus (HSV) and human herpesvirus (HHV) increase infertility rates whilst human papillomavirus (HPV), cytomegalovirus (CMV), and hepatitis B and C virus (HBV, HCV) infections mostly lead to higher abortion and miscarriage rates. Moreover, HPV infection is linked to increased tubal infertility, endometriosis, and pelvic inflammatory disease. HPV was the most frequently observed infection and with lower pregnancy rate and foetal death in women undergoing IVF treatments. Assisted reproductive treatment could be a safe and effective approach for HIV and HBV infected women.

Association analysis of KISS1 polymorphisms and haplotypes with polycystic ovary syndrome.

INTRODUCTION: KISS1 play an essential role in human reproductive functions by regulating the hypothalamic-pituitary-gonadal axis. Loss-of-function mutations in this gene have been frequently identified in patients with different reproductive disorders. We hypothesised links between KISS1 polymorphisms and polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: In order to find links between KISS1 polymorphisms rs4889 C > G, rs12998 G > A, and rs35431622 A > G with PCOS, 770 blood samples were obtained from 385 control and 385 PCOS women. DNA was extracted, and genotyped for KISS1 variants by PCR. RESULTS: rs12998 G > A was linked to PCOS in dominant (p < 0.001), recessive (p < 0.001), co-dominant (p < 0.001), and allelic models (p < 0.001). In addition, rs4889 C > G was linked in recessive, dominant, co-dominant, and allelic models (p < 0.001). rs35431622 A > G was not linked to PCOS. Further analysis indicated that C-G-G haplotype was more common and G-A-G haplotype was less prevalent in cases compared with controls. CONCLUSION: KISS1 variants rs12998 G > A and rs4889 C > G may be linked to the pathophysiology of PCOS.