Dataset Information

Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis.

ABSTRACT: Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22-1.30) and 1.17 (95% CI: 1.14-1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.

SUBMITTER: Huang SQ

PROVIDER: S-EPMC5334725 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis.

Huang Shi-Qi SQ Zhang Na N Zhou Zi-Xing ZX Huang Chui-Can CC Zeng Cheng-Li CL Xiao Di D Guo Cong-Cong CC Han Ya-Jing YJ Ye Xiao-Hong XH Ye Xing-Guang XG Ou Mei-Ling ML Zhang Bao-Huan BH Liu Yang Y Zeng Eddy Y EY Yang Guang G Jing Chun-Xia CX

International journal of environmental research and public health 20170210 2

Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Res ...[more]

PMID: 28208589

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Project description:Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0 x 10?? in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10?² in CelD and < 1 x 10?³ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10?? and 6.39 x 10??, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55 x 10?¹? and 1.38 x 10?¹¹ respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci: PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect.

Dataset Information

Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis.

Publications

Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis.

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