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

PROBLEM: 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. MATERIALS AND METHODS: 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 LHß and V454I and I161K in LHCGR are the most deleterious nsSNPs affecting the structure and function of the protein. CONCLUSION: These SNPs are still uncharacterised; hence providing a baseline for validation of their association with the susceptibility of diseases and develop personalised therapeutics.

Interplay between PCOS and microbiome: The road less travelled.

Polycystic ovarian syndrome (PCOS) is a complicated neuro-endocrinal, reproductive, and metabolic condition. It encompasses patterns such as hyperandrogenism, recurrent cysts triggered by steroidogenic functional aberrations in the ovaries, overweight, chronic inflammation, and more. The underlying cause of this heterogeneous illness is obscure, although it is suspected to be driven by a blend of environmental and hereditary factors. In recent years, the connection between the microbiome and PCOS has been acknowledged and is thought to be involved in the genesis of the syndrome's emergence. Microbiota vary in different pathological features of PCOS, and fundamental pathways linked to their involvement in the commencement of diverse clinical presentations in PCOS open up a new avenue for its management. Prebiotic, probiotic, synbiotic, and fecal-microbiota-transplant, by promoting eubiosis and nullifying the effect caused by the altered microbial profile in PCOS women, can aid in management of diverse phenotypes associated with the syndrome. These microbiota-mediated treatments improve PCOS women's metabolic, inflammatory, and hormonal profiles. However, more studies are needed to elucidate the mechanisms that drive this positive effect.

Epitope based peptide vaccine against SARS-COV2: an immune-informatics approach.

World is witnessing exponential growth of SARS-CoV2 and fatal outcomes of COVID 19 has proved its pandemic potential already by claiming more than 3 lakhs deaths globally. If not controlled, this ongoing pandemic can cause irreparable socio-economic and psychological impact worldwide. Therefore a safe and effective vaccine against COVID 19 is exigent. Recent advances in immunoinformatics approaches could potentially decline the attrition rate and accelerate the process of vaccine development in these unprecedented times. In the present study, a multivalent subunit vaccine targeting S2 subunit of the SARS-CoV2 S glycoprotein has been designed using open source, immunoinformatics tools. Designed construct comprises of epitopes capable of inducing T cell, B cell (Linear and discontinuous) and Interferon γ. physiologically, vaccine construct is predicted to be thermostable, antigenic, immunogenic, non allergen and non toxic in nature. According to population coverage analysis, designed multiepitope vaccine covers 99.26% population globally. 3D structure of vaccine construct was designed, validated and refined to obtain high quality structure. Refined structure was docked against Toll like receptors to confirm the interactions between them. Vaccine peptide sequence was reverse transcribed, codon optimized and cloned in pET vector. Our in-silico study suggests that proposed vaccine against fusion domain of virus has the potential to elicit an innate as well as humoral immune response in human and restrict the entry of virus inside the cell. Results of the study offer a framework for in-vivo analysis that may hasten the process of development of therapeutic tools against COVID 19.Communicated by Ramaswamy H. Sarma.

Association of rs6259 polymorphism with SHBG levels and Poly Cystic Ovary Syndrome in Indian population: a case control study.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. PCOS reflects a number of possible etiologies but its pathophysiology is still unclear. The principal abnormality of the syndrome is hyperandrogenism (70-80%). The access of androgens to target tissues is regulated by sex hormone-binding globulin (SHBG), a transport protein secreted by liver i.e. specific for androgens. Present study was done to find the association of rs6259 polymorphism with SHBG levels and Poly Cystic Ovary Syndrome in Indian population. Present study was a case control study. 400 subjects were enrolled for the study and serum SHBG levels and D327N polymorphism were measured. The D327N polymorphism (wild-type and variant allele) was detected using PCR-RFLP method (restriction enzyme Bbs-I). PCOS group was found to have significantly lower SHBG levels than healthy controls. There was no significant difference in genotype distribution between PCOS and controls (χ2 = 1.0335, p = 0.59). Significant difference in SHBG levels of PCOS and control group highlights the potential of SHBG as a biomarker for PCOS. However, no significant difference in genotype distribution between PCOS and controls provided an insight that rs6259 polymorphism is not associated with the risk of PCOS and SHBG levels.

Evaluating the association of TNF α promoter haplotype with its serum levels and the risk of PCOS: A case control study.

Poly cystic ovary syndrome is the major cause of anovulatory infertility. TNF α, pro-inflammatory cytokine is associated with obesity, insulin resistance and hyperandrogenism, therefore in present study we tried to find the association between TNF α promoter polymorphisms, TNF α levels and the risk of PCOS. Present case control study was carried on 400 women of age 16-40 years. TNF α levels were measured by ELISA whereas promoter polymorphisms were evaluated by PCR-RFLP. Haplotype and Linkage disequilibrium analysis was also done. TNF α level was significantly higher in PCOS group (13.24 ±â€¯9.78) than control (5.5 ±â€¯3.8). Haplotype analysis revealed that GGTCT, AGTCT, AGCCT and AACCT are the susceptible haplotypes associated with TNF α level. rs361525 and rs1799964 were found to be associated with the risk of PCOS (p = 0.0006, 0.015). GGCCT, AATAT, GATAT (most susceptible), AGCCT, GGTCT and GATCT are the susceptible haplotypes for PCOS. Significant difference between TNF α levels in PCOS and Control group suggest it's one of the promising candidates for the marker of inflammation (sensitivity and specificity 91.23 and 94.56% respectively, with area under the curve 0.907 at 95% CI 0.8723-0.9512). Presence of GGCCT haplotype suggests the susceptibility towards PCOS which needs to be further verified. In addition to this, present study not only provides a pavement for the diagnosis, but also monitoring and management of PCOS too.

Comprehensive analysis of damage associated SNPs of MMP9 gene: A computational approach.

Extracellular matrix is a dynamic meshwork of macromolecules that plays an important role in biological processes such as tissue remodeling and various developmental processes. Collagen is the chief component of ECM. Upon hydrolysis, it forms an irreversible left-handed helical structure which is further hydrolyzed by a specialized group of MMP family i.e. Gelatinases (MMP2 and MMP9). Present study was carried to figure out deleterious SNPs associated with MMP9 gene. Our results showed that two nsSNP (rs8125581 and rs41529445) that are present in catalytic domain are highly conserved and affect the protein structure and function.7 SNPs located in UTRs were found to alter miRNA seed region 13 SNPs of splice site were predicted to affect splice signals thereby affecting the post translational expression of MMP9. Most of the SNPs are still uncharacterized thereby present study provides a direction that can help to validate the relation between the altered expressions and functions of MMP9 protein in terms of disease susceptibility.

Comprehensive in-silico prediction of damage associated SNPs in Human Prolidase gene.

Prolidase is cytosolic manganese dependent exopeptidase responsible for the catabolism of imido di and tripeptides. Prolidase levels have been associated with a number of diseases such as bipolar disorder, erectile dysfunction and varied cancers. Single nucleotide polymorphism present in coding region of proteins (nsSNPs) has the potential to alter the primary structure as well as function of the protein. Hence, it becomes necessary to differentiate the potential harmful nsSNPs from the neutral ones. 19 nsSNPs were predicted as damaging by in-silico analysis of 298 nsSNPs retrieved from dbSNP database. Consurf analysis showed 18 out of 19 substitutions were present in the conserved regions. 4 substitutions (D276N, D287N, E412K, and G448R) that observed to have damaging effect are present in catalytic pocket. Four SNPs listed in splice site region were found to affect splicing of mRNA by altering acceptor site. On 3'UTR scan of 77 SNPs listed in SNP database, 9 SNPs were lead to alter miRNA target sites. These results provide a filtered data to explore the effect of uncharacterized nsSNP and SNP related to UTRs and splice site of prolidase to find their association with the disease susceptibility and to design the target dependent drugs for therapeutics.

Plasma prolidase levels as a biomarker for polycystic ovary syndrome.

AIM: Assessment of plasma prolidase levels in polycystic ovary syndrome (PCOS). PATIENTS & METHODS: PCOS patients were screened according to Rotterdam Criterion and prolidase levels were measured. RESULTS: A total of 170 patients and 160 controls were recruited for the study and it was found that prolidase levels were significantly higher in PCOS group (991.10 ± 39.52) than control (621.89 ± 23.94). Furthermore it has been found that prolidase levels increase with the number of cysts in ovaries. CONCLUSION: Significant difference between prolidase levels in PCOS and control shows that it may be used as a diagnostic marker for disease. In addition to this, there is a positive correlation found between prolidase levels and number of cysts, hence may be used as a prognostic marker to monitor disease status.