Search

Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α –308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α –308 G>A gene polymorphism with CRC risk. Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association. Results: The pooled analysis indicated no risk associated with TNF-α –308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863–1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688–2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843–1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849–1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686–2.033). Subgroup analysis revealed that TNF-α –308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias. Conclusions: No association of TNF-α –308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α –308 G>A SNP in the etiology of CRC and to endorse the present findings.

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

Background: Earlier studies have shown that interlukin-10 (IL-10) -1082 A>G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility. Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous (GG vs. AA: P=0.889; OR = 1.029, 95% CI = 0.692–1.529), heterozygous (GA vs. AA: P=0.244; OR = 0.906, 95% CI = 0.767–1.070), dominant (GG + AG vs. AA: P=0.357; OR = 1.196, 95% CI = 0.817–1.752), and recessive (GG vs. AA + AG: P=0.364; OR = 0.921, 95% CI = 0.771–1.100) genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P=0.004; OR = 1.694, 95% CI = 1.183–2.425) demonstrated increased risk of PTB in Caucasian population. Conclusions: This meta-analysis concludes that IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population.

Purpose: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. Methods: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. Results: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689–1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499–1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603–1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625–1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542– 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718–0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673–0.928) of the mixed population. Conclusions: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.

BsmI (rs1544410) polymorphism located in intron 8 at the 3′-end of the vitamin D receptor (VDR) gene is known to be involved in the regulation of mRNA stability. Many studies evaluated the possible correlation between VDR BsmI polymorphism and the risk of pulmonary tuberculosis (PTB), and reported conflicting results. In the present study, an updated meta-analysis was performed to evaluate the above-said association. PubMed, Embase, and Google Scholar web-databases were searched for the relevant studies and a meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models. A total of 19 studies comprising 3644 controls and 2635 cases were included in the present study. Overall no association of PTB in allelic contrast (b compared with B: P=0.285; OR =0.909, 95% CI =0.762–1.083), homozygous (bb compared with BB: P=0.881; OR =0.975, 95% CI =0.700–1.359), heterozygous (bB compared with BB: P=0.834; OR =1.017, 95% CI =0.872–1.185), dominant (bb compared with BB + Bb: P=0.451; OR =0.954, 95% CI =0.843–1.079) and recessive (bb + Bb compared with BB: P=0.983; OR =1.002, 95% CI =0.868–1.156) genetic models in comparison with wild-type allele and genotype BB were observed. However, variant allele (b compared with B: P=0.001; OR =2.289, 95% CI =1.661–3.154) showed increased risk of PTB in Asians. In conclusion, VDR BsmI polymorphism is not a risk factor for PTB in overall population. However, this polymorphism may be interrelated to an increased risk of PTB amongst Asians.