Association between risk of asthma and gene polymorphisms in CHI3L1 and CHIA: a systematic meta-analysis

Abstract

Background: Previous studies have indicated that chitinase 3-like 1 (CHI3L1) gene rs4950928 polymorphism and acidic mammalian chitinase (AMCase or CHIA) gene rs10494132 polymorphism are associated with the risk of asthma. However, the results are inconsistent because of small sample size and varied ethnicity and age in studies. Therefore, a systematic meta-analysis was important to clarify the effect of CHI3L1 rs4950928 polymorphism and CHIA rs10494132 variant on asthma risk.

Methods: An electronic literature search was conducted to identify all the eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and sensitivity analysis as well as publication bias were assessed to investigate the associations. All statistical analyses were performed using STATA 12.0.

Results: Eight published articles with 10 case-control studies were included, 5 studies were of CHI3L1 rs4950928 polymorphism and another 5 studies involved CHIA rs10494132 polymorphism. Overall, no significant association was found between CHI3L1 polymorphism and asthma susceptibility. After stratified according to ethnicity, CHI3L1 rs4950928 variant was associated with decreased asthma risk in Caucasians (GG + GC vs. CC: OR = 0.621, 95% CI = 0.484-0.797, P = 0.000; GC vs. CC: OR = 0.612, 95% CI = 0.470-0.796, P = 0.000; G vs. C: OR = 0.696, 95% CI = 0.567-0.856, P = 0.001). When stratified population by age, there was no association in children under all genetic models. As for CHIA rs10494132 polymorphism, no evidence of association between CHIA rs10494132 polymorphism and asthma risk was identified. Furthermore, subgroup analysis by ethnicity revealed a positive correlation between CHIA rs10494132 polymorphism and asthma risk among Asians (TT vs. TC + CC: OR = 1.476, 95% CI = 1.071-2.032, P = 0.017; T vs. C: OR = 1.326, 95% CI = 1.024-1.717, P = 0.032). Additionally, in the subgroup analysis conducted according to age, CHIA rs10494132 variant was also found to be associated with the increased risk of asthma in children (TT vs. TC + CC: OR = 1.472, 95% CI = 1.067-2.030, P = 0.019; T vs. C: OR = 1.320, 95% CI = 1.016-1.713, P = 0.037).

Conclusions: The G allele of CHI3L1 rs4950928 might be a protective factor against the development of asthma. However, the rs10494132 polymorphism of CHIA might be a risk factor for asthma.

Keywords: Asthma; CHI3L1; CHIA; Gene polymorphism; Meta-analysis.

Fig. 1

Flowchart of study selection procedure

Fig. 2

Forest plot of the association between CHI3L1 rs4950928 polymorphism and asthma risk by ethnicity stratification under (a) the dominant model (GG + GC vs. CC), (b) the codominant model (GC vs. CC) and (c) the allele model (G vs. C)

Fig. 3

Forest plot of the association between CHIA rs10494132 polymorphism and asthma risk stratified by ethnicity under (a) the recessive model (TT vs. TC + CC) and (b) the allele model (T vs. C)

Fig. 4

Forest plot of the association between CHIA rs10494132 polymorphism and asthma risk by age stratification under (a) the recessive model (TT vs. TC + CC) and (b) the allele model (T vs. C)

Fig. 5

Begg’s funnel plots of publication bias for the association between CHI3L1 rs4950928 (a) and CHIA rs10494132 (b) polymorphisms and asthma risk under the recessive models (GG vs. GC + CC; TT vs. TC + CC)