Endocrine Abstracts

Background: Polycystic ovary syndrome (PCOS) is a common disorder, yet not fully understood. Multiple hormonal and metabolic factors influence the pathophysiology of disease; resulting in various phenotypic characteristics among PCOS population. The luteinizing hormone/choriogonadotropin receptor (LHCGR, OMIM: 152790) is a G protein- coupled receptor mapped on chromosome 2p16.3; its coding region comprises 10 exons separated by 10 introns which transcript to protein with 699 amino acids.

Objectives: To determine genetic mutations of LHCGR gene in Sudanese families affected by PCOS.

Methods: A prospective laboratory based cross-sectional study was implemented to examine genetic mutations in LHCGR 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), enzymatic methods and partial selected exon 11 from in silico analysis data were analyzed by polymerase chain reaction (PCR) for polymorphism detection followed by Sanger sequencing for genotyping among selected families.

Results: From the In silico analysis, we revealed that the most (29) distributed SNPs were located through LHCGR coding region. Thereafter, we select exon 11 which contain the most reported SNPs and Sanger sequencing revealed normal sequence of exon 11 of LHCGR gene that were statistically correlated with serum LH, Testosterone and insulin levels among PCOS families and characterized by homozygous inheritance mode. The PCOS 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).

Conclusion: This is the first molecular family-based study in Sudan exploring the genetics of the LHCGR gene in women manifesting PCOS. These novel mutations give further information about the genetic inheritance and may explain some of the altered ovarian function and responses in women with PCOS. Keywords: PCOS, Luteinizing hormone, SNPs, infertility, family studies, LHCGR