IL-1RN and IL-1βPolymorphism and ARV-Associated Hepatotoxicity

Abstract

The severity of hepatic injury depends upon cytokines. Previous studies associated IL-1RN allele 2 with IL-1β production. Hence, we examined the association of IL-1 RN and IL-1β polymorphisms with ARV-associated hepatotoxicity. Genotyping of IL-1RN (VNTR), IL-1β (-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR = 1.41, P = 0.25; OR = 1.67, P = 0.31). IL-1β-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR = 3.74, P = 0.05). IL-1β-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR = 1.80, P = 0.90). IL-1β-511CT and -511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR = 2.29, P = 0.27; OR = 2.64, P = 0.19). IL-RN 2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR = 1.42, P = 0.64, OR = 8.79, P = 0.09). IL-1β-511CT and -511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR = 4.29, P = 0.20; OR = 1.95, P = 0.56). IL-1β-511CT and -511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR = 2.56, P = 0.26; OR = 2.84, P = 0.24). IL-1β-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

Mechanistic insights into antiretroviral drug‐induced liver injury

“…103 However, exposure to a combination of EFV and isoniazid resulted in increased oxidative and nitrosative stress, leading to the formation of membrane permeability transition, and ultimately necrotic cell death. 73 These data demonstrated that a combination of drugs causing hepatotoxicity can induce mitochondrial dysfunction, leading to necrotic cell death.…”

“…The immune system plays a critical role in augmenting and mediating some of the adverse reactions such as DILI and hypersensitivity reactions. Studies have incriminated polymorphisms in cytokine genes 68,73,74 and the HLA [75][76][77][79][80][81]86,87 that predispose-HIV-infected individuals to adverse reactions to ART. There is a paucity of studies dissecting the contribution of different immune subsets in the pathogenesis of DILI in HIV-infected patients that are on therapy.…”

Micro RNA in Degenerative Disorders

“…However, the primer sequences for TNF-α were F: 5′-GCCACCACGC-TCTTCTG--3'and R: 5′-GCAGCCTTGTCCCTTGA according to Li et al [23]. IL-1β gene primer sequences were F: 5'-TTGTGGCTGTGGAGAAGC-TG-3' and R: 5' CCAGTTGTTGACCAAAGGCTTTT-3' according to Singh et al [24]. IL-6 specific primer sequences were F: 5'-TCTCTCCGCAAGAGACTTCCA-3' and R: 5'-ATACTGGTCTGTTGTG-GGTGG-3' according to Singh et al [24].…”

“…IL-1β gene primer sequences were F: 5'-TTGTGGCTGTGGAGAAGC-TG-3' and R: 5' CCAGTTGTTGACCAAAGGCTTTT-3' according to Singh et al [24]. IL-6 specific primer sequences were F: 5'-TCTCTCCGCAAGAGACTTCCA-3' and R: 5'-ATACTGGTCTGTTGTG-GGTGG-3' according to Singh et al [24]. miRNA 146 a specific primer sequences were F: 5'-UGAGAACUGAAUUC-CAUGGGUU-3' and R: 5'-ACCUGUGAA-GUUCAGUUCUUU -3' according to Yamasaki et al [25].Primer sequences of F: 5'-CATTATTACTTTTGGTACGCG-3' and R: 5'-GTCGTATCCAGTGCGTGTC-GTG-3' were used for miRNA 126 gene according to Huang et al [10].…”

First insights into the molecular basis association between promoter polymorphisms of the IL1B gene and Helicobacter pylori infection in the Sudanese population: computational approach

“…Genetic variations in the promoter region of genes encoding cytokines were shown to correlate with individual differences in the expression of respective cytokines which may in uence the intensity of the in ammatory response and susceptibility to many diseases (31)(32)(33)(34)(35). IL-1B gene has two allelic variants (CT; dbSNP: rs16944) and (TC; dbSNP: rs1143627) which are located at positions -511 and -31, respectively, in the promoter region.…”