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Meta-analysis of the association between NLRP1 polymorphisms and the susceptibility to vitiligo and associated autoimmune diseases.

ABSTRACT: Genetic variants are linked to vitiligo and associated autoimmune diseases. We performed a meta-analysis to evaluate the effects of the rs12150220, rs2670660, and rs6502867 polymorphisms within the human NLR Family Pyrin Domain Containing 1 (NLRP1) gene. We initially identified 1,306 candidate articles through literature searches of Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane in July 2017. After strict screening, we included 19 eligible case-control studies, and analyzed the data using Stata/SE 12.0 software. No difference between vitiligo cases and controls was detected for NLRP1 rs12150220, rs2670660, or rs6502867 under most genetic models [P_association (P value of association test) > 0.05). With regard to vitiligo-associated autoimmune diseases, like Addison's disease, type 1 diabetes, or systemic lupus erythematosus, a decreased risk was detected for rs12150220 in the Caucasian subgroup under all models [P_association < 0.05, odds ratio (OR) < 1]. No relationships were observed for other polymorphisms, including rs2670660, rs6502867, and the "A-A, G-T, G-A, A-T" haplotypes of rs2670660/rs12150220 (P_association > 0.05). This meta-analysis demonstrates that within the Caucasian population, the NLRP1 rs12150220 polymorphism may correlate with a decreased risk of vitiligo-associated autoimmune diseases, especially autoimmune Addison's disease, type 1 diabetes, or systemic lupus erythematosus.

SUBMITTER: Li J

PROVIDER: S-EPMC5675702 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Meta-analysis of the association between <i>NLRP1</i> polymorphisms and the susceptibility to vitiligo and associated autoimmune diseases.

Li Juan J Yan Min M Zhang Yuan Y Feng Chao C Wang Huicong H Wang Cuiyu C Sun Li L

Oncotarget 20170922 50

Genetic variants are linked to vitiligo and associated autoimmune diseases. We performed a meta-analysis to evaluate the effects of the rs12150220, rs2670660, and rs6502867 polymorphisms within the human NLR Family Pyrin Domain Containing 1 (<i>NLRP1</i>) gene. We initially identified 1,306 candidate articles through literature searches of Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane in July 2017. After strict screening, we included 19 eligible case-control studies, and analyz ...[more]

PMID: 29152150

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Project description:PurposeAzathioprine (AZA) is widely used as an immunosuppressive drug in autoimmune diseases, but its use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating AZA therapy. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and AZA-induced ADRs using meta-analysis.MethodsWe explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and AZA-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in patients with autoimmune diseases were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using Revman 5.3 software.ResultsEleven published studies, with a total of 651 patients with autoimmune diseases, investigated associations between TPMT polymorphisms and AZA-induced ADRs, were included in this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with AZA-induced overall ADRs, bone marrow toxicity and gastric intolerance; pooled ORs were 3.12 (1.48-6.56), 3.76 (1.97-7.17) and 6.43 (2.04-20.25), respectively. TPMT polymorphisms were not associated with the development of hepatotoxicity; the corresponding pooled OR was 2.86 (95%CI: 0.32-25.86). However, the association in GI subset could be driven by one single study. After this study was excluded, the OR was 2.11 (95%CI: 0.36-12.42); namely, the association became negative.ConclusionsOur meta-analysis demonstrated an association of TPMT polymorphisms with overall AZA-induced ADRs, bone marrow toxicity and gastric intolerance, but not with hepatotoxicity. The presence of the normal TPMT genotypes cannot preclude the development of ADRs during AZA treatment, TPMT genotyping prior to commencing AZA therapy cannot replace, may augment, the current practice of regular monitoring of the white blood cell. Because of small sample sizes, large and extensive exploration was required to validate our findings.

Dataset Information

Meta-analysis of the association between NLRP1 polymorphisms and the susceptibility to vitiligo and associated autoimmune diseases.

Publications

Meta-analysis of the association between <i>NLRP1</i> polymorphisms and the susceptibility to vitiligo and associated autoimmune diseases.

Similar Datasets

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