School Of Health Sciences

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/102

Browse

Has files: NoSubject: search.filters.subject.genetic association

Search Results

Now showing 1 - 2 of 2
  • 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
    A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans
    (BioMed Central Ltd, 2021-07-27T00:00:00) Bejar, Cynthia A.; Goyal, Shiwali; Afzal, Shoaib; Mangino, Massimo; Zhou, Ang; van der Most, Peter J.; Bao, Yanchun; Gupta, Vipin; Smart, Melissa C.; Walia, Gagandeep K.; Verweij, Niek; Power, Christine; Prabhakaran, Dorairaj; Singh, Jai Rup; Mehra, Narinder K.; Wander, Gurpreet S.; Ralhan, Sarju; Kinra, Sanjay; Kumari, Meena; de Borst, Martin H.; Hypp�nen, Elina; Spector, Tim D.; Nordestgaard, B�rge G.; Blackett, Piers R.; Sanghera, Dharambir K.
    Context: Multiple observational studies have reported aninverse relationship between 25-hydroxyvitaminD concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results ofshort- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have beeninconsistent. Objectives and methods: To evaluate the causal role of reduced blood25(OH)D in T2D, here we have performed a bidirectional Mendelian randomizationstudy using 59,890 individuals (5,862 T2D cases and 54,028 controls) fromEuropean and Asian Indian ancestries. We used six known SNPs, including threeT2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluatethe causality and direction of the association between T2D and circulating25(OH)D concentration. Results: Results of the combined meta-analysis of eightparticipating studies showed that a composite score of three T2D SNPs wouldsignificantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 � 10�32; Z score 11.86, which, however, hadno significant association with 25(OH)D status (Beta -0.02nmol/L � SE0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the geneticallyinstrumented composite score of 25(OH)D lowering alleles significantlydecreased 25(OH)D concentrations (-2.1nmol/L � SE 0.1nmol/L,p = 7.92 � 10�78; Z score -18.68) but was notassociated with increased risk for T2D (OR 1.00, p = 0.12;Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as anindividual genetic instrument, a per allele reduction of 25(OH)D concentration(-4.2nmol/L � SE 0.3nmol/L)was predicted to increase T2D risk by 5%, p = 0.004;Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GCrs2282679, CYP2R1 rs12794714) when used as an individual instrument. Conclusion: Our new data on this bidirectional Mendelianrandomization study suggests that genetically instrumented T2D risk does notcause changes in 25(OH)D levels. However, genetically regulated 25(OH)Ddeficiency due to vitamin D synthesis gene (DHCR7) may influence the risk ofT2D. � 2021, The Author(s).