Dataset Information

LRBA Gene Polymorphisms and Risk of Coal Workers' Pneumoconiosis: A Case-Control Study from China.

ABSTRACT: The lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) is a member of the WDL-BEACH-WD (WBW) gene family. Defects in this gene are associated with the disordered autoimmunity in various diseases, including pulmonary fibrosis. In this study, we investigated the association between the functional polymorphisms in LRBA and risk of coal workers' pneumoconiosis (CWP) in a Chinese population. Three potentially functional polymorphisms (rs2290846, rs3749574, and rs1782360) in LRBA were genotyped and analyzed in a case-control study, including 703 CWP cases and 705 controls. Genotyping was performed by the ABI 7900HT Real Time PCR system. Our results suggested that genotype rs2290846 AA was significantly associated with decreased risk of CWP (Adjusted OR = 0.61, 95% CI = 0.41-0.92), and the recessive model also supported the protective role of the genotype (Adjusted OR = 0.60, 95% CI = 0.40-0.89). Further, the polymorphism of rs2290846 decreased the CWP risk among cases over 27 years of dust exposure (adjusted OR = 0.51, 95% CI = 0.28-0.94) and non-smokers (adjusted OR = 0.58, 95% CI = 0.34-1.00). A potential role of rs2290846 AA has been proposed by expression quantitative trait loci (eQTL) and The Cancer Genome Atlas (TCGA). The present results suggest that LRBA SNPs are associated with CWP susceptibility in a Chinese population. Further studies focused on detailed mechanism or larger cohorts are warranted to validate our findings.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5664639 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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LRBA Gene Polymorphisms and Risk of Coal Workers' Pneumoconiosis: A Case-Control Study from China.

Liu Yi Y Yang Jingjin J Wu Qiuyun Q Han Ruhui R Yan Weiwen W Yuan Jiali J Ji Xiaoming X Li Yan Y Yao Wenxi W Ni Chunhui C

International journal of environmental research and public health 20170927 10

The lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) is a member of the WDL-BEACH-WD (WBW) gene family. Defects in this gene are associated with the disordered autoimmunity in various diseases, including pulmonary fibrosis. In this study, we investigated the association between the functional polymorphisms in <i>LRBA</i> and risk of coal workers' pneumoconiosis (CWP) in a Chinese population. Three potentially functional polymorphisms (rs2290846, rs3749574, and rs1782360) in < ...[more]

PMID: 28953250

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Project description:The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population.We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C?>?T alleles on the expression of IL-17A.Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR?=?0.43, 95 % CI?=?0.23-0.83) and rs8193036 TT (adjusted OR?=?0.59, 95 % CI?=?0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI?=?0.13-0.86 for rs3748076; adjusted OR?=?0.41, 95 % CI?=?0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR?=?0.45, 95 % CI?=?0.21-0.98 for rs3748076; adjusted OR?=?0.46, 95 % CI?=?0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR?=?0.42, 95 % CI?=?0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C?>?T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study.The rs3748067 G?>?A and rs8193036 C?>?T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.

Dataset Information

LRBA Gene Polymorphisms and Risk of Coal Workers' Pneumoconiosis: A Case-Control Study from China.

Publications

LRBA Gene Polymorphisms and Risk of Coal Workers' Pneumoconiosis: A Case-Control Study from China.

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