Dataset Information

Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China.

ABSTRACT: BACKGROUND: Tuberculosis (TB) is a contagious disease affected by multiple genetic and environmental factors. Several association studies have suggested that cellular immune response is vital for controlling and preventing of tuberculosis infection. Low molecular weight polypeptides (LMPs) and transporters with antigen processing (TAPs) are the main molecules in the processing and presentation pathway for intracellular antigens. This study was performed to elucidate whether these antigen-processing genes (LMP/TAP) polymorphisms could be associated with the risk of tuberculosis infection in China. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 205 active pulmonary tuberculosis patients and 217 normal controls from Li population for this study. Four polymorphisms of LMP/TAP genes were determined by PCR-RFLP assay and haplotypes were constructed by software PHASE 1.0. Of the total four polymorphisms, genotype frequencies of LMP7 AA homozygote and CA heterozygote were significantly greater among cases compared to controls, with odds ratio of 3.77 (95% CI: 1.60-8.89; P = 0.002) and 2.97 (95% CI: 1.80-4.90; P<0.0001), respectively. The genotypes of TAP1-2 GG homozygote and AG heterozygote were more frequent in subjects with TB than in controls, with odds ratio of 3.94 (95% CI: 1.82-8.53; P = 0.001) and 2.87 (95% CI: 1.75-4.71; P<0.0001), respectively. Similarly, we found that haplotype B which carried LMP7 and TAP1-2 variations significantly increased the susceptibility to TB (OR = 3.674, 95% CI: 2.254-5.988; P<0.0001). Moreover, it is noteworthy that the homozygote of wild haplotype A (A/A) may be a strong protection for TB infection. CONCLUSIONS: Our findings suggested that LMP/TAP gene polymorphisms might be risk factors for TB infection among Li population in China.

SUBMITTER: Wang D

PROVIDER: S-EPMC3299725 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China.

Wang Danmei D Zhou Yue Y Ji Limin L He Tong T Lin Feng F Lin Rong R Lin Tangchang T Mo Yanna Y

PloS one 20120312 3

<h4>Background</h4>Tuberculosis (TB) is a contagious disease affected by multiple genetic and environmental factors. Several association studies have suggested that cellular immune response is vital for controlling and preventing of tuberculosis infection. Low molecular weight polypeptides (LMPs) and transporters with antigen processing (TAPs) are the main molecules in the processing and presentation pathway for intracellular antigens. This study was performed to elucidate whether these antigen- ...[more]

PMID: 22427944

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Project description:Tuberculosis (TB) is an important public health problem. Studies indicated that TAP plays a key role in the presentation and transport of antigenic peptides during anti-M.tb infection. Given the important biological role of the TAP gene involved in anti-M.tb infection, a family-based case-control study including 133 tuberculosis patients, 107 healthy household contacts, and 173 healthy controls was conducted to assess the association between TAP gene polymorphisms and TB susceptibility. The basic information of subjects and their blood samples were collected. Four SNPs including rs1135216, rs1057141, rs241447, and rs3819721 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results suggested that BMI, residence, bedroom crowding, indoor humidity, fitness activities, history of smoking, and TB exposure history were associated with the occurrence of tuberculosis (P < 0.05). A significant association was observed between the TAP1 rs1135216 CT/CC genotype and increased TB risk, and the ORs were 2.56 (95% CI 1.31-4.99) and 6.73 (95% CI 1.33-34.02), respectively. TAP2 rs3819721 GG genotype carriers also showed an increased risk of TB when compared TB patients to healthy household contacts. Haplotype analysis revealed that the haplotype CT at rs1057141 and rs1135216 (OR = 11.34, 95% CI 1.49-86.56; OR = 7.45, 95% CI 1.43-38.76), as well as TA at rs241447 and rs3819721 (OR = 2.20, 95% CI 1.07-4.56) had a significantly increased risk of TB. The genetic risk scores (GRS) analysis of the four loci indicated that the risk of tuberculosis increased with increasing GRS scores in TB vs HHC (Ptrend = 0.010) and in TB vs HC (Ptrend = 0.001). In conclusion, our findings suggested that the SNPs of rs1135216 and rs3819721 were associated with TB susceptibility among the tuberculosis-prone families in the Chinese Han population and the risk of developing tuberculosis increases with the number of risk alleles, which could help identify high-risk groups in time and take scientific preventive measures. Further cohort studies with large samples are needed to validate the role of TAP gene variants on TB susceptibility.

Dataset Information

Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China.

Publications

Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China.

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