CHI3L1 polymorphisms associate with asthma in a Taiwanese population.

Yishan Tsai,Tsunai Wang,Mingshyan Huang,Jianing Li,Chaochien Wu,Yunxuan Chen,Yuting Tseng,Yingchin Ko,Chinchou Wang,Mengchih Lin

doi:10.1186/1471-2350-15-86

Abstract

BackgroundA 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.MethodsWe 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.ResultsAdjusted 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.ConclusionsOur findings suggest that the CHI3L1 polymorphisms rs1538372 and rs10399931 can be used as genetic markers for predicting asthma risk in the Taiwanese population.

Highlights

A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility
We investigated the differences in clinical quantitative traits, including adiposity, serum levels of immunoglobulin E (IgE) and YKL-40, and lung function, among subjects with CHI3L1 rs1538372 and rs10399931 genotypes in asthmatic patients and control groups
We found that FEV1% and forced vital capacity (FVC)% decreased by 12.37% (P = 0.03) and 12.10% (P = 0.036), respectively, as YKL40 levels were higher in CHI3L1 rs1538372 CC carriers than in TC or TT carriers

Summary

Introduction

A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility. Asthma has a complicated etiology, including airway inflammation, bronchial hyper-responsiveness, and a variable degree of airway obstruction that is influenced by environmental [1] and genetic factors [2]. This disease impacts more than 300 million people worldwide and has detrimental effects on the quality of life [3]. The third 18 glycosyl hydrolase family member, YKL40, is encoded by the chitinase 3-like 1 (CHI3L1) gene located on chromosome 1q32.1 ( called human cartilage gp-39/HcGp-39 or breast regression protein 39/BRP-39) [5,6]. Novel functions of YKL-40 are mediated by the Th2-inflammation pathway, which was fully demonstrated in BRP-39 gene knockout mice and YKL-40 transgenic mice [8]

Methods

Results

Conclusion