IRGM rs13361189 polymorphism may contribute to susceptibility to Crohn’s disease: A meta-analysis

Abstract

The aim of the present meta-analysis was to evaluate the correlation between a common polymorphism, rs13361189 C>T in the immunity-related GTPase M (IRGM) gene, and susceptibility to Crohn’s disease (CD). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library and CBM databases were investigated from database inception through to October 1, 2013 without the application of any language restrictions. The meta-analysis was performed using STATA 12.0 software and the relative risk (RR) with a 95% confidence interval (CI) was calculated. Seven case-control studies were included with a total of 3,093 CD patients and 3,227 healthy control subjects. The results of the meta-analysis revealed that the IRGM rs13361189 polymorphism correlates with an increased risk of CD (T allele versus C allele: RR=1.25 with 95% CI, 1.04–1.50; P=0.016 and CT + TT versus CC: RR=1.21 with 95% CI, 1.03–1.42; P=0.018). A subgroup analysis conducted using a genotyping method indicated that the IRGM rs13361189 polymorphism was correlated with an increased risk of CD in the TaqMan® (T allele versus C allele: RR=1.32 with 95% CI, 1.01–1.73; P=0.042) and the polymerase chain reaction-restriction fragment length polymorphism subgroups (T allele versus C allele: RR=1.80 with 95% CI, 1.32–2.45; P<0.001 and CT + TT versus CC: RR=1.61 with 95% CI, 1.19–2.18; P=0.018). However, no correlation was observed in the direct sequencing subgroup (P>0.05). Further subgroup analysis by sample size demonstrated significant correlations between the IRGM rs13361189 polymorphism and an increased risk of CD in the large sample-size subgroup (T allele versus C allele: RR=1.46 with 95% CI, 1.26–1.68; P<0.001 and CT + TT versus CC: RR=1.40 with 95% CI, 1.21–1.62; P<0.001). However, no correlation was identified between the IRGM rs13361189 polymorphism and CD risk in the small sample-size subgroup (P>0.05). The present meta-analysis indicated that the IRGM rs13361189 polymorphism may contribute to susceptibility to CD. Thus, IRGM rs13361189 polymorphism may be a potential biomarker for the early diagnosis of CD.

Crohn’s disease IRGM risk alleles are associated with altered gene expression in human tissues

“…We found that homozygous minor allele status at rs13361189 and rs10065172 were both (as expected given their very high LD) associated with increased risk for CD, but not for UC. Like us, several prior reports have found an association of rs13361189 with CD risk (3,15,27,32,36,38,41,44,47). On the other hand, rs10065172 has been found to associate with CD in some (15,36,41), but not all (27) studies.…”

Association between angiotensinogen T174M polymorphism and ischemic stroke: A meta-analysis

“…The most likely reason for the inconsistencies among these studies is that they are single case-control studies with small sample sizes. [ 18 ] The aim of meta-analysis is to combine the same kind of studies to increase the sample size and statistical power, and thereby get a more authentic result.…”

Race-specific association of an IRGM risk allele with cytokine expression in human subjects

“…rs13361189 has also been associated with leprosy 20 and autoimmune thyroid disease 21 , and rs10065172 with tuberculosis 22 and sepsis mortality 23 , collectively suggesting that IRGM regulates a wide spectrum of human disease. A major limitation of the studies performed to date on IRGM and CD risk, however, is that nearly all have been conducted in Europeans 17 , 24 , 25 . Compared to Europeans, Africans have much higher IRGM expression and IRGM rs13361189 risk (C) allele frequency (~ 0.50 vs. 0.10 [useast.ensembl.org]), and much lower LD of rs13361189 to the upstream CNV deletion 16 .…”