Comprehensive Analysis of Damage Associated SNPs of Luteinizing Hormone and Its Receptor: A Computational Approach.

Abstract

The luteinizing hormone (LH), produced by gonadal and nongonadal cells in the anterior pituitary gland play a critical role in human sexual development and reproduction. It is required for the induction of ovulation in females and sex steroid hormone production in both males and females. It is also an important player in early pregnancy events in oviducts and in absence of LH signalling, the uterus cannot initiate pregnancy. LH works through its receptor LHCGR. Therefore, it is quite important to figure out those mutations that have the potential to affect the structure and function of both LH and LHR. Various in silico tools were employed in the study for the data mining of SNPs and predicting their possible impact on the structure and function of the protein. ConSurf analysis predicted V454I and I161K are exposed residues in the 2D structure of protein and highly conserved in protein structure. PSIPRED and Swiss Modeller were employed to predict the 2D and 3D structure of mutated receptor protein. FT site server predicted both substitutions were involved in the ligand-binding site RESULTS: By present analysis, we have found that R59G in LHα, Q74R and T78N in LHβ and V454I and I161K in LHCGR are the most deleterious nsSNPs affecting the structure and function of the protein. These SNPs are still uncharacterised; hence providing a baseline for validation of their association with the susceptibility of diseases and develop personalised therapeutics.