Systematic review and meta-analysis of the association between IL18RAP rs917997 and CCR3 rs6441961 polymorphisms with celiac disease risks

Abstract

Objectives: We performed a systematic review and meta-analysis to estimate the polymorphism effects of IL18RAP and CCR3 on celiac disease susceptibility. Methods: PubMed and Web of Science databases were searched (to June 2015) on IL18RAP rs917997 and CCR3 rs6441961 polymorphisms. Results: The meta-analysis included 16 and 7 studies for rs917997 and rs6441961, respectively. The minor risk A allele at both rs917997 and rs6441961 carried risks (odds ratios) of 1.24 (95% CI 1.18–1.31) and 1.21 (95% CI 1.12–1.31), respectively. These alleles contributed to increase risks in all celiac disease patients by 5.04 and 6.35%. The estimated lambdas were 0.73 and 0.51, suggesting that an additive model would be the best choice for both gene effects. Conclusions: This meta-analysis provides robust estimates that IL18RAP rs917997 and CCR3 rs6441961 are potential risk factors for celiac disease in European populations. Studies are needed to confirm these findings in different ethnicities.

Keywords:

• CCR3
• celiac disease
• genetic association studies
• IL18RAP
• meta-analysis

Financial & competing interests disclosure

The authors were supported in part by funding from the National Natural Science Foundation of China (grant No. 30901249; 81101267), the Guangdong Natural Science Foundation (grant No. 10151063201000036; S2011010002526), Guangdong Province Medical Research Foundation (Grant No. A2014374) and the Project from Jinan University (grant No. 21612426, 21615427). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors would like to thank Ammarin Thakkinstian, Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand; John R. Thompson, Department of Health Sciences, University of Leicester, UK.; Sasivimol Rattanasiri, Section of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand for providing the statistical computing algorithm support.

Key issues

• A number of studies have identified the IL-18 receptor accessory proteins gene (IL18RAP) in 2q12 and the chemokine (C-C motif) receptor 3 gene (CCR3) in 3p21 with celiac disease susceptibility in different European populations; however, the results are inconsistent. We performed a systematic review and meta-analysis of IL18RAP and CCR3 associated with celiac disease.

• IL18RAP rs917997 and CCR3 rs6441961 are potential risk factors for celiac disease in European populations. Individuals carrying the minor A allele in rs917997 and rs6441961 had 24 and 21% increased risks of developing celiac disease than those carrying the major G allele, respectively.

• Further studies must be directed toward the specific functional implication of this finding.

Notes