title: Identification of genetic associations of SP110/MYBBP1A/RELA with pulmonary tuberculosis in the Chinese Han population.
abstract: Genetic factors play important roles in the development of tuberculosis (TB). SP110 is a promising candidate target for controlling TB infections. However, several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB have yielded conflicting results. This may be partly resolved by studying other genes associated with SP110, such as MYBBP1A and RELA. Here, we genotyped 6 SP110 SNPs, 8 MYBBP1A SNPs and 5 RELA SNPs in 702 Chinese pulmonary TB patients and 425 healthy subjects using MassARRAY and SNaPshot methods. Using SNP-based analysis with Bonferroni correction, rs3809849 in MYBBP1A [Pcorrected (cor) = 0.0038] and rs9061 in SP110 (Pcor = 0.019) were found to be significantly associated with TB. Furthermore, meta-analysis of rs9061 in East Asian populations showed that the rs9061 T allele conferred significant risk for TB [P = 0.002, pooled odds ratio (OR), 1.24, 95% confidence interval (CI) = 1.08-1.43]. The MYBBP1A GTCTTGGG haplotype and haplotypes CGACCG/TGATTG within SP110 were found to be markedly and significantly associated with TB (P = 2.00E-06, 5.00E-6 and 2.59E-4, respectively). Gene-based analysis also demonstrated that SP110 and MYBBP1A were each associated with TB (Pcor = 0.011 and 0.035, respectively). The logistic regression analysis results supported interactions between SP110 and MYBBP1A, indicating that subjects carrying a GC/CC genotype in MYBBP1A and CC genotype in SP110 possessed the high risk of developing TB (P = 1.74E-12). Our study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel marker for identifying the risk of developing TB in the Chinese Han population.
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200030, China. cailei2010@126.com
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Shao-Li
authors.initials: SL
authors.lastname: Deng
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yue
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Wan
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D012307:Risk Factors; D051996:Transcription Factor RelA / Q000235:genetics*; D014157:Transcription Factors; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; C498143:RELA protein, human; D016601:RNA-Binding Proteins; C412425:Sp110 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors