title: SFRP1 variations influence susceptibility and immune response to Mycobacterium tuberculosis in a Chinese Han population.
abstract: OBJECTIVE
  SFRP1 acts as a well-established inhibitory regulator of the Wnt signaling pathway, whose polymorphisms have been demonstrated to be associated with the risk of inflammation, infection as well as cancer. We verified the hypothesis that single nucleotide polymorphisms (SNPs) within SFRP1 gene are associated with susceptibility and clinical characteristics of tuberculosis disease in a Chinese Han population.
  
  
  METHODS
  Six candidate SNPs were genotyped using MassARRAY method in a case-control design (260 tuberculosis patients and 252 healthy controls). A comprehensive analysis of single locus including the genotypic, allelic frequencies and the genetic models, haplotypic construction as well as gene-gene interaction was conducted to investigate the relationships between SNPs and TB. Significant SNPs were further interrogated in relation to TB clinical features and host inflammatory status.
  
  
  RESULTS
  Genotype frequencies of rs4736958 and rs7832767 within SFRP1 gene were significantly different (p=0.011, p=0.008, respectively) between tuberculosis group and control group. Subjects carrying C allele for rs4736958 showed a decreased tuberculosis risk (OR=0.66, 95% CI=0.51-0.87, p=0.003), whereas individuals carrying rs7832767 T allele had a significant increased risk in tuberculosis susceptibility (OR=1.32, 95% CI=1.01-1.74, p=0.046). Genetic model analysis revealed that dominant, co-dominant and recessive models of rs4736958 were associated with decreased susceptibility to tuberculosis (p all <0.05), while the recessive and co-dominant models of rs7832767 were related to significantly increased risk for tuberculosis (p all <0.05). There was a reduced tuberculosis risk in association with the haplotype CC (representing rs3242 and rs4736958) of SFRP1 (OR=0.73, 95% CI=0.56-0.96, p=0.026). Further stratification analysis indicated that TB patients with genotype CT for rs4736958 were associated with higher CRP concentrations, and heterozygous patients (CT genotype) of rs7832767 trended towards greater ESR levels.
  
  
  CONCLUSIONS
  SNPs rs4736958 and rs7832767 of SFRP1 gene were significantly associated with tuberculosis susceptibility and might influence the expression levels of inflammatory markers of tuberculosis patients in a Chinese Han population.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 909607093@qq.com.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 515262192@qq.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 804876291@qq.com.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 18200139080@163.com.
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 992717469@qq.com.
authors.forename: Mengqiao
authors.initials: M
authors.lastname: Shang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 494267197@qq.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: zhouyi2011@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: songxingbo1981@163.com.
authors.forename: Xingbo
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: luxiaojun1972@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: docbwy@126.com.
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.affiliation: Division of Pulmonary Disease, Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: 384481688@qq.com.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D001426:Bacterial Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C513697:CRP protein, Mycobacterium tuberculosis; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins
keywords: Inflammatory markers; Secreted frizzled-related protein 1 (SFRP1); Single nucleotide polymorphisms (SNPs); Tuberculosis