School Of Health Sciences
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Item Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis(Mary Ann Liebert Inc., 2023-10-25T00:00:00) Sharma, Priya; Singh, Abhilash Kumar; Senapati, Sabyasachi; Kapoor, Harmanpreet Singh; Goyal, Lajya Devi; Kaur, Balpreet; Kamra, Pooja; Khetarpal, PreetiGenetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case�control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00�1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97�3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13�1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78�0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS. � Mary Ann Liebert, Inc.Item Genetic variants of metabolism and inflammatory pathways, and PCOS risk �Systematic review, meta-analysis, and in-silico analysis(Elsevier B.V., 2023-09-14T00:00:00) Sharma, Priya; Bhatia, Kabir; Singh Kapoor, Harmanpreet; Kaur, Balpreet; Khetarpal, PreetiImportance: Identification of genetic risk factors for PCOS susceptibility. Objective: To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways. Data sources: Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2. Main outcomes: Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk. Results: Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795. Conclusion: and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations. � 2023 Elsevier B.V.Item Assessment of Serum Elements Concentration and Polycystic Ovary Syndrome (PCOS): Systematic Review and Meta-analysis(Springer, 2022-01-14T00:00:00) Sharma, Priya; Gupta, Vartika; Kumar, Kush; Khetarpal, PreetiChange in the levels of trace elements has been linked with PCOS pathogenesis by various studies, whereas some had reported no such association. Therefore, in order to evaluate association of eleven trace element (Cu, Zn, Cr, Cd, Se, Mn, Fe, Mg, Co, Ni and Pb) serum concentration with PCOS pathogenesis, current systematic review and meta-analysis has been carried out. Literature search was conducted using PubMed, Central Cochrane Library, Google Scholar and Science Direct databases with appropriate keywords. Studies published upto 3rd of September were evaluated for eligibility with suitable inclusion and exclusion criteria. Only case�control studies examining the association of serum trace element concentrations between PCOS cases and controls were selected. Present meta-analysis identified 32 articles with 2317 PCOS and 1898 controls. The serum Cu (MD = 15.40; 95% CI = 4.32 to 26.48; p = 0.006), Co (MD = 0.01; 95% CI = 0.01 to 0.02; p = 0.000), Cr (MD = 0.04; 95% CI = 0.00 to 0.07; p = 0.03) and Fe (MD = 12.98; 95% CI = 5.87�20.09; p = 0.0003) concentration is significantly higher, while lower concentration has been observed for Se (MD = ? 0.99; 95% CI = ? 1.31 to ? 0.67; p = 0.000) and Mg (MD = ? 223.41; 95% CI = ? 391.60 to ? 55.23; p = 0.009) among women with PCOS in comparison with the healthy group. Concentration of other elements which were analysed is not significantly related to PCOS. In short, PCOS women has higher serum concentrations of Cu, Co, Cr and Fe and lower concentrations of Se and Mg. Studies with sub-population of obese, non-obese and with and without insulin resistance are important to understand the pathomechanism of these elements in the syndrome. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Increased incidence of spontaneous abortions on exposure to cadmium and lead: a systematic review and meta-analysis(Taylor and Francis Ltd., 2021-06-25T00:00:00) Kaur, Mandeep; Sharma, Priya; Kaur, Rajinder; Khetarpal, PreetiBackground: Spontaneous abortions are the most severe complication of early pregnancy and are a major reproductive health problem. Although this could be caused due to various cytogenetic, immunological, or endocrinological reasons, role of environmental toxicants cannot be ruled out. In order to explore the role of cadmium and lead in causing spontaneous abortions, current systematic review and meta-analysis had been carried out. Methodology: Literature search was performed using appropriate keywords in PubMed, Science Direct, Cochrane Library, and Google Scholar databases up to December 25 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Metananalysis was carried out with the help of RevMan software (version 5.3). Results: Meta-analysis of nine studies on cadmium concentrations in blood of women with at least one spontaneous abortions and controls revealed standardized mean difference (SMD)=3.39, 95% CI (2.17, 4.61), with p <.05. Similarly, meta-analysis of eight studies on lead concentrations revealed standardized mean difference (SMD)=6.24, 95% CI (4.34, 8.14), with p <.05. Conclusion: Populations exposed to heavy metals such as cadmium and lead are at higher risk of pregnancy loss. Therefore, couples experiencing repeated pregnancy losses may be screened for heavy metal load. � 2021 Informa UK Limited, trading as Taylor & Francis Group.Item CYP19 gene rs2414096 variant and differential genetic risk of polycystic ovary syndrome: a systematic review and meta-analysis(Taylor and Francis Ltd., 2020-08-28T00:00:00) Sharma, Priya; Kaur, Mandeep; Khetarpal, PreetiBackground: Previously, many studies investigated the association between CYP19 rs2414096(G > A) and susceptibility to develop PCOS. However, results had been inconsistent. Therefore, our systematic review and meta-analysis aimed to identify the association between CYP19 rs2414096 and PCOS risk. Methods: A systematic literature search was done from database PubMed, Google Scholar, Science Direct, and Cochrane Library up to July 15 2020 and statistical analysis was performed by RevMan5.3. Results: A total of seven studies comprised of 1414 PCOS cases and 1276 controls were included in the current meta-analysis. The pooled analysis showed that overall, there is a significant association between CYP19 rs2414096(G > A) and risk of PCOS (OR = 0.74, 95% CI= 0.62�0.88, p =.0008). In dominant model, GG + AG vs GG and recessive genetic model AA vs AG + GG found a significant association (OR = 1.60,95% CI = 1.10�2.31, p =.01; OR = 0.65,95% CI = 0.45�0.93, p =.02) respectively which indicates that GG phenotype might be risk factor for PCOS development. In stratified subgroup analysis, there was significant association between CYP19 rs2414096 polymorphism and PCOS risk for non-Indian population only while no association was found with Indian population. Conclusion: Present meta-analysis studies indicate that CYP19 rs2414096 is associated with PCOS risk and important in pathogenesis of PCOS for many populations but for Indian population more studies are required as Indian population comprises of various subpopulations genetically isolated since long. � 2020 Informa UK Limited, trading as Taylor & Francis Group.