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CHI3L1 polymorphisms associate with asthma in a Taiwanese population.

ABSTRACT: A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility. CHI3L1, which encodes the YKL-40 protein, is associated with asthma in Western European and American populations and with atopy in a Korean population. However, asthma-associated polymorphisms remain unknown for a Taiwanese population.We enrolled 628 adult asthmatic patients and 1:1 age-sex matched community-based controls in southern Taiwan and performed a combined effect sizes analysis to test if CHI3L1 polymorphisms were related to genetic risks for asthma in the Asian population. Ten tagSNP polymorphisms for the CHI3L1 gene were selected from the HapMap database and genotyped using a TaqMan allelic discrimination assay.Adjusted odds ratios of the CHI3L1 rs1538372 CC genotype (aOR?=?1.97, 95% CI: 1.23-3.14) and the rs10399931 GG genotype (aOR?=?1.77, 95% CI: 1.13-2.77) were significantly associated with asthma in the Taiwanese populations. Predictive values of forced expiratory volume in the first second of the forced vital capacity (12.37%, P?=?0.03) and of forced vital capacity (12.10%, P?=?0.036) decreased in conjunction with an increase in YKL-40 levels among CHI3L1 rs1538372 CC carriers; these values were 16.1% (P?=?0.004) and 14.5% (P?=?0.011), respectively, among CHI3L1 rs10399931 GG carriers. Furthermore, steroid use by asthma patients did not affect serum YKL-40 levels, but both polymorphisms had significant effects on YKL-40 levels in asthma patients who used steroids.Our findings suggest that the CHI3L1 polymorphisms rs1538372 and rs10399931 can be used as genetic markers for predicting asthma risk in the Taiwanese population.

SUBMITTER: Tsai Y

PROVIDER: S-EPMC4113488 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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CHI3L1 polymorphisms associate with asthma in a Taiwanese population.

Tsai Yishan Y Ko Yingchin Y Huang Mingshyan M Lin Mengchih M Wu Chaochien C Wang Chinchou C Chen Yunxuan Y Li Jianing J Tseng Yuting Y Wang Tsunai T

BMC medical genetics 20140723

<h4>Background</h4>A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility. CHI3L1, which encodes the YKL-40 protein, is associated with asthma in Western European and American populations and with atopy in a Korean population. However, asthma-associated polymorphisms remain unknown for a Taiwanese population.<h4>Methods</h4>We enrolled 628 adult asthmatic patients and 1:1 age-sex matched community-based controls in southern Taiwan and ...[more]

PMID: 25056157

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Project description:BackgroundPrevious 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.MethodsAn 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.ResultsEight 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).ConclusionsThe 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.

Project description:YKL-40 is a chitinase-like glycoprotein encoded by the chitinase 3-like 1 gene, CHI3L1, localized at chromosome 1q32.1. Increased levels of serum YKL-40 have been reported to be a biomarker for asthma and a reduced lung function. Interestingly, the C-allele of the -131 C-->G (rs4950928) polymorphism of CHI3L1 has been shown to associate with bronchial hyperresponsiveness and reduced lung function suggesting that variations in CHI3L1 may influence risk of asthma. The objective of the present study was to investigate the association of common variation in the CHI3L1 locus with asthma, atopy and lung function in a large population-based sample of adults.Eleven single nucleotide polymorphisms (SNPs) of CHI3L1 including rs4950928 were genotyped in 6514 individuals. Asthma was defined as self-reported history of physician-diagnosed asthma. Total IgE and specific IgE to inhalant allergens were measured on serum samples. Lung function was measured by spirometry. Homozygosity of the rs4950928 G allele as compared to homozygosity of the C allele was associated with self-reported physician diagnosed asthma (OR 1.5 (95% CI, 1.00-2.26)) and with prevalence of atopic asthma (OR 1.93 (95% CI, 1.21-3.07)) after adjustment for age, sex, smoking status, socio-economic class and BMI. Carriers of rs883125 G allele had a significantly lower prevalence of atopy (OR 0.82 (CI, 0.72; 0.94)) as compared to homozygosity of the C allele. None of the SNPs examined were significantly associated with FEV1. However, two SNPs (rs10399931 and rs4950930) appeared to be significantly associated with FEV(1)/FVC-ratio. Subgroup analyses of never-smokers did not consistently influence the associations in an either positively og negatively way.In contrast to previous studies, the rs4950928 G allele, and not the C allele, was found to be associated with asthma. A few other SNPs of the CHI3L1 was found to be significantly associated with atopy and FEV1/FVC ratio, respectively. Thus, more studies seem warranted to establish the role of CHI3L1 gene in asthma and atopy.

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CHI3L1 polymorphisms associate with asthma in a Taiwanese population.

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CHI3L1 polymorphisms associate with asthma in a Taiwanese population.

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