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Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese.

ABSTRACT: Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR]?=?1.57, 95% confidence interval [CI] 1.30-1.91, P?=?1.3?×?10-6). Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR?=?1.54, 95% CI 1.27-1.87, P?=?4.2?×?10-6; global haplotype association P?=?3.5?×?10-5). Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR?=?1.56, 95% CI 1.29-1.90, P?=?1.4?×?10-6). Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk.

SUBMITTER: Liu C

PROVIDER: S-EPMC5095599 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese.

Liu Cheng C He Tao T Rong Yanxiao Y Du Fengjiao F Ma Dongxing D Wei Yujie Y Mei Zhiqin Z Wang Yuling Y Wang Haibin H Zhu Yuehua Y Zhang Zongde Z Zheng Li L Wu Xueqiong X Liu Huiliang H Ding Wenjun W

Scientific reports 20161104

Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chi ...[more]

PMID: 27812036

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Project description:BackgroundImmune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population.MethodsWe performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis.ResultsWe observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB.ConclusionsThis study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.

Project description:ObjectivesMannose-binding lectin (MBL) is an important component of innate immunity. Structural and promoter polymorphisms in the MBL2 gene that are responsible for low MBL levels are associated with susceptibility to infectious diseases. The objective of this study was to investigate the association of serum MBL levels and MBL2 polymorphisms with persistent Staphylococcus aureus bacteremia (SAB) in adult Korean patients.MethodsWe conducted a case-control study nested in a prospective cohort of patients with SAB. The study compared 41 patients with persistent bacteremia (?7 days) and 46 patients with resolving bacteremia (<3 days). In each subject, we genotyped six single-nucleotide polymorphisms in the promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (alleles A/B, A/C, and A/D) of the MBL2 gene and measured serum MBL concentrations. We also compared MBL2 genotypes between SAB patients and healthy people.ResultsPatients with persistent bacteremia were significantly more likely to have low/deficient MBL-producing genotypes and resultant low serum MBL levels, than were patients with resolving bacteremia (P?=?0.019 and P?=?0.012, respectively). Independent risk factors for persistent bacteremia were metastatic infection (adjusted odds ratio [aOR], 34.7; 95% confidence interval [CI], 12.83-196.37; P?=?0.003), methicillin resistance (aOR, 4.10; 95% CI, 3.19-29.57; P?=?0.025), and low/deficient MBL-producing genotypes (aOR, 7.64; 95% CI, 4.12-63.39; P?=?0.003). Such genotypes were significantly more common in patients with persistent bacteremia than in healthy people (OR, 2.09; 95% CI, 1.03-4.26; P?=?0.040).ConclusionsThis is the first demonstration of an association of low MBL levels and MBL2 polymorphisms responsible for low or deficient MBL levels with persistent SAB. A combination of factors, including clinical and microbiological characteristics and host defense factors such as MBL levels, may together contribute to the development of persistent SAB.

Project description:ObjectiveTuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL polymorphisms and TB has been studied in various populations, the results are controversial. The aim of this study was to investigate mannose-binding lectin (MBL) gene polymorphisms with susceptibility to pulmonary tuberculosis (PTB) in a Lur population of Iran.MethodsIn this case-control study, four functional MBL gene polymorphisms (HL, XY, PQ and AB) were genotyped by using PCR Single Strand Conformation Polymorphism (SSCP) technique in a Lur population living in Lorestan Province, consisting of 100 patients with pulmonary tuberculosis (PTB) age and sex matched 100 healthy controls (HCs). Association analyses were performed with the SPSS 21 statistical software.ResultsWe found that MBL (HH) genotype polymorphism significantly was associated with increased susceptibility to TB (35% in patients vs. 22% in controls, P = 0.0417, OR = 1.909, %95 CI = 1.020-3.573). Additionally, H allele showed a significant association with increased risk of TB (56.5% in patients vs. 46% in controls, P = 0.0357, OR = 1.525, %95 CI = 1.028-2.262). Also, the distribution of L allele in patients was significantly lower frequency in TB patients compared to controls (43.5% vs. 54%, P = 0.0357, OR = 0.656, %95 CI = 0.442-0.973). However, the allelic and genotypic frequencies of AB, XY and PQ polymorphisms were not significantly different between the patients and the controls. We couldn't detect any significant differences between haplotypes among TB patients and healthy controls.ConclusionsOur findings demonstrated that HH genotype and H allele may increase the susceptibility to pulmonary TB in the Lur population of Iran, although L allele may decrease the susceptibility to pulmonary TB in this population. We suggest that it is necessary to further more studies with larger sample size and other ethnic population.

Dataset Information

Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese.

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Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese.

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