The revelation of Novel Mutations in Human Luteinizing Hormone Beta Subunit Related to Polycystic Ovary Syndrome among Sudanese Women

IntroductionPolycystic ovary syndrome (PCOS) is a common disorder that is not fully understood. Multiple hormonal and metabolic factors impact on disease pathophysiology resulting in various phenotypic characteristics among the PCOS population. Luteinizing hormone beta subunit (LHB) (protein ID P01229) is mapped on (chr19p13.3) and consists of three exons. Luteinizing hormone (LH) has a central role in stimulation ovarian steroidogenesis, in particular androgen production, and the promotion of ovulation. ObjectivesTo determine if genetic variations of LHB are associated with PCOS among Sudanese families. MethodsA prospective laboratory based cross-sectional study to examine genetic mutations in LHB that associate with PCOS in families (cases; n=35 families, 90 females and controls; n=11 families, 30 females) in Khartoum State, Sudan. Quantitative enzyme linked immuno-sorbent assay (ELISA) and polymerase chain reaction (PCR) with Sanger sequencing were used to analyze biochemical parameters and detect polymorphisms. Protein structure and function bioinformatics analysis was conducted using standard software. ResultsPCOS cases had significantly different biochemical parameters from the controls (LH: p<0.001; testosterone: p<0.001; fasting glucose: p=0.02; insulin: p=0.01; triglycerides: p=0.03; total cholesterol: p<0.001; high density lipoprotein (HDL): p=0.012;low density lipoprotein (LDL): p<0.001). There were no differences in follicle stimulating hormone (FSH) (p=0.984) or prolactin (p=0.068). Sanger sequencing revealed 5 single nucleotide polymorphisms (rs5030775, A18T; rs746167425, R22K; rs1800447, W28R; rs35270001, H30R; and rs34349826, I35T) located on (exon 2) of LHB gene that were statistically correlated with serum LH, Testosterone and insulin levels among PCOS families. ConclusionThis is the first molecular family-based study in Sudan exploring the genetics of the LHB gene in women manifesting PCOS. These novel mutations give further information about the role of genetic inheritance and may explain some of the altered ovarian function and responses in women with PCOS.