Department Of Human Genetics And Molecular Medicine

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/103

Browse

Subject: search.filters.subject.meta-analysis

Search Results

Now showing 1 - 6 of 6
  • No Thumbnail Available
    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, Preeti
    Genetic 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.
  • No Thumbnail Available
    Item
    A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease
    (Frontiers Media S.A., 2023-01-19T00:00:00) Shree, Tanya; Banerjee, Pratibha; Senapati, Sabyasachi
    Purpose: As an immune-modulator, vitamin D is known to regulate immune response and is implicated in disease pathogenesis. Celiac disease (CD) is a systemic autoimmune disease and susceptibility conferred by vitamin D metabolism is under investigation. Studies on the association of vitamin D metabolism and genetic polymorphisms are expected to explain CD pathogenesis. We performed a systematic review�based meta-analysis to investigate the 25(OH)D serum levels and susceptibility conferred by the genetic variants of VDR in CD. Methods: Systematic review was conducted through a web-based literature search following stringent study inclusion�exclusion criteria. The Newcastle�Ottawa Scale and GRADE tools were used to assess the quality of evidence in studies and the study outcome. Cohen's ? value was estimated to access the reviewer's agreement. RevMan 5.4.1 was used to perform the meta-analyses. Weighted mean difference and Meta p-value was assessed for 25(OH)D serum levels. Meta-odds ratio and Z-test p-value were evaluated to estimate the allelic susceptibility of VDR variants. Results: A total of 8 out of 12 studies were evaluated for �25(OH)D� serum level, while four studies were found eligible for SNPs (Bsm1, Apa1, Fok1, and Taq1) of VDR. Significantly higher levels [WMD = 5.49, p < 0.00001] of 25(OH)D were observed in healthy controls than in patients with CD. rs2228570-T (Fok1) [Meta-OR = 1.52, p = 0.02] was confirmed to be predisposing allele for CD. Conclusion: Reduced serum level of 25(OH)D and association of Fok1 T-allele of VDR confirmed in this study plays a critical role in immunomodulation and maintaining barrier integrity, which is majorly implicated in CD. Copyright � 2023 Shree, Banerjee and Senapati.
  • No Thumbnail Available
    Item
    Meta-analysis confirmed genetic susceptibility conferred by multiple risk variants from CTLA4 and SERPINA1 in granulomatosis with polyangiitis
    (John Wiley and Sons Inc, 2022-06-03T00:00:00) Banerjee, Pratibha; Kumar, Uma; Khetarpal, Preeti; Senapati, Sabyasachi
    Background: Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well-powered genetic investigations. We performed a systematic review based meta-analysis in GPA to investigate the genetic susceptibility conferred by non-human leukocyte antigen (non-HLA) candidate genes. Methods: A systematic review was performed using web-based literature search and eligible studies were included following inclusion-exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle-Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's ? value. Meta-analyses were performed using RevMan 5 tool. Meta-odds ratio (meta-OR) and Z test P value were evaluated to estimate the genetic susceptibility for each of the variants. Results: Eighteen studies were found eligible and 7 genetic variants from only 4 genes, namely CTLA4, PRTN3, SERPINA1 and PTPN22 could be studied for meta-analysis. rs231775-G (49-G) (Meta-OR�=�1.42 [1.14-1.76]; P�=.001) of CTLA4 and rs7151526-A (Meta-OR�=�2.70 [1.51-4.85]; P�=.0008) of SERPINA1 were confirmed to be predisposing alleles, and rs5742909-C (318-C) (Meta-OR�=�0.65 [0.44-0.97]; P�=.03) of CTLA4 was found to be protective for GPA. In concordance with the genetic association of rs7151526-A, serological marker for the same variant �Z� allele of SERPINA1 was found to be predisposing (Meta-OR�=�12.60 [5.01-31.68]; P <.00001) for GPA. Conclusion: Genetic variants confirmed in this study play critical roles in T-cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management. � 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
  • No Thumbnail Available
    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, Preeti
    Background: 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.
  • No Thumbnail Available
    Item
    Multiple allelic associations from genes involved in energy metabolism were identified in celiac disease
    (Springer, 2021-06-23T00:00:00) Bhagavatula, Sandilya; Banerjee, Pratibha; Sood, Ajit; Midha, Vandana; Thelma, B.K.; Senapati, Sabyasachi
    Energy metabolism is a critical factor that influences disease pathogenesis. Recent high-throughput genomic studies have enabled us to look into disease biology with greater details. Celiac disease (CD) is an inflammatory autoimmune disease where ~60 non-HLA genes were identified which in conjunction with HLA genes explain ~55% of the disease heritability. In this study we aimed to identify susceptibility energy metabolism genes and investigate their role in CD. We re-analysed published Immunochip genotyping data, which were originally analysed for CD association studies in north Indian and Dutch population. 269 energy metabolism genes were tested. Meta-analysis was done for the identified SNPs. To validate the functional implications of identified markers and/or genes, in silico functional annotation was performed. Six SNPs were identified in north Indians, of which three markers from two loci were replicated in Dutch. rs2071592 (PMeta=5.01e?75) and rs2251824 (PMeta=1.87e?14) from ATP6V1G2-NFKBIL1-DDX39B locus and rs4947331 (PMeta= 9.85e?13) from NEU1 locus were found significantly associated. Identified genes are key regulators of cellular energy metabolism and associated with several immune mediated diseases. In silico functional annotation showed significant biological relevance of these novel markers and genes. FDI approved therapeutics against ATP6V1G2 and NEU1 are currently in use to treat chronic and inflammatory diseases. This study identified two pathogenic loci, originally involved in energy metabolism. Extensive investigation showed their synergistic role in CD pathogenesis by promoting immune mediated enteric inflammation. Proposed CD pathogenesis model in this study needs to be tested through tissue-on-chip and in vivo methods to ensure its translational application. � 2021, Indian Academy of Sciences.
  • No Thumbnail Available
    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, Preeti
    Background: 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.