title: No Significant Effect of ASAP1 Gene Variants on the Susceptibility to Tuberculosis in Chinese Population.
abstract: Recent studies have proposed that the ASAP1 gene participates in regulating the adaptive immune response to Mycobacterium tuberculosis infection. A GWAS study has reported that ASAP1 polymorphisms (rs4733781 and rs10956514) were associated with the risk of tuberculosis (TB) in Russians. But due to population heterogeneity, different races would have different causative polymorphisms, and the aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of the ASAP1 gene and TB risk in Chinese population.A total of 7 SNPs in the ASAP1 gene were genotyped in 1115 Western Chinese Han and 914 Tibetan population using an improved multiplex ligation detection reaction (iMLDR) method. The associations of SNPs with TB risk and clinical phenotypes were determined based on the distributions of allelic frequencies and different genetic models. A meta-analysis was carried out to further assess the relationship between ASAP1 polymorphism and TB risk.Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant associations with the risk of TB via analyses of a single locus, haplotype, and subgroup differences. Meta-analysis showed no evidence supporting association between rs10956514 and overall risk for TB. Subsequent analysis referring to the genotypes of SNPs in relationship to clinical phenotypes identified that rs4236749 was associated with different serum C-reactive protein levels, suggesting a role of this locus in influencing the inflammatory state of Western Chinese Han patients with TB.Our present data revealed that ASAP1 polymorphisms are unlikely to confer susceptibility to TB in the Western Chinese Han and Tibetan populations, which challenges the promising roles of the ASAP1 gene in the development of TB and highlights the importance of validating the association findings across ethnicities.
authors.affiliation: From the Department of Laboratory Medicine (XH, WP, ZZ, JZhang, JZhou, BC, JC, YZ, XL, BY) and Division of Tuberculosis (XC), West China Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hu
authors.forename: Wu
authors.initials: W
authors.lastname: Peng
authors.forename: Xuerong
authors.initials: X
authors.lastname: Chen
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Bei
authors.initials: B
authors.lastname: Cai
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000235:genetics*
chemical_list: C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002097:C-Reactive Protein