Genetic variants at 18q11.2 and 8q24 identified by genome-wide association studies were not associated with pulmonary tuberculosis risk in Chinese population.

OBJECTIVE: Genome-wide association study (GWAS) recently identified several susceptibility loci in ASAP1 gene on chromosome 8q24 for tuberculosis (TB) in a Russian population, but no relevant studies have been performed to validate these findings. In addition, previous GWAS in Ghana and Gambia found that the variant rs4331426 at 18q11.2 was a susceptibility locus for TB. However, the follow-up studies reported conflicting results. Herein, we investigated the contribution of genetic variants at 8q24 and 18q11.2 to TB in Chinese population. METHODS: We genotyped four genetic variants at 8q24 (rs10956514 and rs11774633) and 18q11.2 (rs4331426 and rs6507226) in a case-control study with 355 newly bacteriologically confirmed pulmonary TB cases and 395 healthy controls using TaqMan allelic discrimination assay. Subsequently, we conducted a meta-analysis including 4 reported studies in Chinese populations and our case-control study with a total of 3118 cases and 3226 controls to further evaluate the relationship between rs4331426 at 18q11.2 and TB risk. RESULTS: We did not find significant association between genetic variants at 8q24 and risk of TB (rs10956514: OR=0.89, 95%CI: 0.72-1.09, P=0.253; rs11774633: OR=0.86, 95%CI: 0.69-1.08, P=0.206). We did not observe significant association for genetic variants at 18q11.2 (rs4331426: OR=0.62, 95%CI: 0.34-1.14, P=0.122; and rs6507226: OR=0.98, 95%CI: 0.80-1.20, P=0.853). Moreover, the pooled results from the Meta-analysis further supported that rs4331426 at 18q11.2 was not associated with TB risk in Chinese population (OR=0.90, 95% CI: 0.63-1.29). CONCLUSIONS: Our findings indicate that TB risk-associated loci at 8q24 and 18q11.2 identified by GWAS from the other populations may not contribute to TB susceptibility in Chinese population.

Association between the CD209 promoter -336A/G polymorphism and susceptibility to tuberculosis: a meta-analysis.

BACKGROUND AND OBJECTIVE: Dendritic cell-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), encoded by the CD209 gene, is a major Mycobacterium tuberculosis receptor on human dendritic cells. The potentially functional -336A/G polymorphism in the CD209 promoter region has been associated with susceptibility to tuberculosis (TB), but the results have been inconclusive. We performed a meta-analysis to clarify the relationship between the CD209-336A/G variant and the risk of TB. METHODS: Ten studies involving a total of 2598 TB patients and 2614 control subjects were systematically reviewed, and the data were quantitatively synthesized by meta-analysis. The Q-test was applied to assess the heterogeneity of associations among the studies, and Egger's regression test was used to assess potential publication bias. RESULTS: No significant association was identified between the CD209-336A/G polymorphism and risk of TB (G allele vs A allele: odds ratio (OR) 1.02, 95% confidence interval (CI) 0.90-1.15). Moreover, no significant association was observed in populations of African ethnicity (OR 1.01, 95% CI 0.87-1.17) or among individuals who were negative for the human immunodeficiency virus (OR 0.98, 95% CI 0.84-1.15). CONCLUSIONS: This meta-analysis has indicated that the CD209-336A/G polymorphism may not contribute to susceptibility to TB.

Meta-analysis on the association of TIRAP S180L variant and tuberculosis susceptibility.

The missense variant S180L in TIRAP (Toll-interleukin-1 receptor domain-containing adaptor protein) gene is implicated in attenuating TLRs signal transaction and may affect individual response to Mycobacterium tuberculosis infection. Several studies investigated the association between TIRAP S180L and risk of tuberculosis (TB), but the results were controversial. In this study, we quantitatively synthesized nine studies relevant to the association between TIRAP S180L polymorphism and TB risk with total 6584 TB cases and 7294 controls using meta-analysis. We found that the variant allele Leu180 and heterozygous genotype Ser/Leu were not significantly associated with risk of TB (allelic OR = 0.99, 95%CI: 0.88-1.11; Ser/Leu vs Ser/Ser: OR = 0.99, 95%CI: 0.87-1.13) with heterogeneity P values > 0.05. In subgroup analysis, none of the significant associations were observed for S180L and TB risk in Africans (allelic OR = 0.58, 95%CI: 0.29-1.61; heterozygous OR = 0.65, 95%CI: 0.32-1.32) or Asians (allelic OR = 1.30, 95%CI: 0.97-1.74; heterozygous OR = 1.17, 95%CI: 0.84-1.65) or risk of pulmonary tuberculosis (PTB) (allelic OR = 0.92, 95%CI: 0.69-1.22; heterozygous OR = 0.98, 95%CI: 0.86-1.12). This meta-analysis indicates that TIRAP S180L polymorphism is unlikely to substantially contribute to TB susceptibility.