Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case–control studies

Abstract

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.

Advances in the Immunology and Genetics of Leprosy

“…Moreover, the most frequently involved SNP of TNF in infectious diseases, TNF-308 G>A (rs1800629), has been widely studied in leprosy with different ethnicities, including Nepalese, Brazilians, and Indians (115,141,142). However, these studies obtained inconsistent results for the association of TNF-308 G>A with leprosy, which inspired a meta-analysis of 14 studies on this topic (143). The meta-analysis found that no association was observed in the overall population or in Asians, but TNF-308 G>A showed a protective effect against leprosy risk in the Latin American population (143).…”

“…However, these studies obtained inconsistent results for the association of TNF-308 G>A with leprosy, which inspired a meta-analysis of 14 studies on this topic (143). The meta-analysis found that no association was observed in the overall population or in Asians, but TNF-308 G>A showed a protective effect against leprosy risk in the Latin American population (143). For LTA of this region, a fine linkage disequilibrium mapping study discovered that LTA+80 A allele was significantly associated with leprosy risk (144).…”

Association of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population

“…Studies with monozygotic/dizygotic twins, family, population-based designs, and more recently, genome-wide association studies (GWAS) and whole exome sequencing (WES) have pinpointed single nucleotide polymorphisms (SNPs) in genes that have been consistently replicated in different populations [2][3][4][5][6]. There is evidence that NOD2, LRRK2, TLR1, TNF, IFNG, IL10, IL23R, TYK2 and PACRG/PRKN (formerly PARK2), which are genes that participate in autophagy and recognition pathways, regulating the host innate immune response are associated with leprosy susceptibility, reaction or its clinical forms [6][7][8][9][10][11][12][13][14][15][16][17][18]. However, genetic association of SNPs in major genes that modulate the immune response need independent replication in different ethnic groups to confirm leprosy outcome [19].…”

Association of TNF (rs1800629) promoter polymorphism and schistosomiasis with sub‐microscopic asymptomaticPlasmodium falciparuminfections in a schistosomiasis‐endemic area in Zimbabwe

“…falciparum infection such as host genetic polymorphisms [2, 8, 9]. Tumour necrosis factor (TNF) (rs1800629) [previously known as TNF‐α or TNFA] [10] polymorphism is thought to be a critical factor in malaria pathogenesis and in the control of parasitaemia [11]. TNF is a pleiotropic cytokine that acts as a pyrogenic and pro‐inflammatory molecule, produced as a part of the host defence against the infection and is involved in the killing of P. falciparum .…”

“…The more common and ancestral TNF1 allele, also referred to as 308.1 allele, has a guanine (G) residue, whereas the less common or alternative allele TNF2 allele, also referred to as 308.2, has an adenine (A) at position 308 of rs1800629 gene promoter. The alternate allele TNF2 has previously been associated with particular manifestations of infectious and non‐infectious diseases [10]. This raises the question of whether variation in the TNF (rs1800629) polymorphism may explain differences in phenotypes related to malaria infections.…”