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Background: MDR1 is involved in the transport of numerous drugs. Polymorphism of MDR1 is linked with the treatment outcome. ARV regimen is being used to manage the progression of HIV infection. Ethnic disparities have been observed in the distribution of MDR1 genotypes. Methods: MDR1 polymorphism (1236 C/T, 3435 C/T) was genotyped in 34 individuals with ARV-associated hepatotoxicity, 131 HIV-infected, and one-fifty-five healthy by utilization of PCR-RFLP. Results: Haplotype TC exposed the greater risk for hepatotoxicity severity when compared between individuals with hepatotoxicity and HIV infected (OR=1.96, P=0.06). While haplotypes TT and CC bared a reduce risk for hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). Haplotype TT and CC displayed a decrease risk of hepatotoxicity severity while compared between individuals with hepatotoxicity and healthy (OR=0.09, P=0.003; OR=0.34, P=0.03). A higher occurrence of MDR1 1236TT genotype was seen among patients with hepatotoxicity who consumed alcohol (28.6% versus 14.8%, OR=1.50). In patients with hepatotoxicity taking nevirapine, there was an increased incidence of MDR1 1236TT genotype in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). In HIV-infected people taking nevirapine, MDR1 1236CT, 1236TT genotypes found to be increased compared with efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). A higher occurrence of MDR1 1236TT genotype has happened in hepatotoxicity cases having both alcohol and nevirapine (40.0% versus 16.67%, OR=2.21). Conclusion: MDR1 haplotypes may have an influence on the severity of hepatotoxicity. Individual utilizing nevirapine and alcohol with MDR1 1236TT and 3435CT genotypes may have combined effect on vulnerability of severity of hepatotoxicity and progression of HIV infection

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Background: Toll-like receptors (TLRs) act as mediators of an innate immune response to infectious agents. The risk for chronic infection and the development of cancer can be potentially influenced by the genetic variations in the TLR genes. TLR3 and TLR7 genes have been associated with susceptibility to several infections and immune diseases. Human population is very diverse. There are significant variations in the TLR3 and TLR7 polymorphisms among ethnic groups. Variations within the population are associated with the disease outcome. Hence, we aimed to compare the occurrence of TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms among healthy individuals of various populations. Method: Genotyping TLR3 (rs5743312 C/T, rs3775296 C/A, and rs3775291 C/T) and TLR7 (rs179009 and rs179008) polymorphisms were done in 158 healthy controls from Western India by utilization of PCR-RFLP. Result: In our study population, the prevalence of TLR3 rs5743312 CC, CT, and TT genotypes were found to be 67.1%, 31.0%, and 1.9%, respectively, whereas genotype distribution of rs3775296 C/A polymorphism was 65.2%, 31.6%, and 3.2%, respectively, and rs3775291C/T was 59.5%, 32.3% and 8.2%, respectively. The occurrence of TLR7 rs179008AA, rs179008AT, rs179008TT genotypes and rs179008A, rs179008T alleles in the healthy individuals were found to be 81.0%, 16.5%, 2.5% and 89.24%, 10.75%, respectively. The prevalence of TLR7 rs179009AA, rs179009AG, rs179009GG genotypes and rs179009A, rs179009G alleles in healthy individuals were 63.3%, 29.1%, 7.6% and 63.3%, 36.7%, respectively. The frequency of TLR7 polymorphism was compared with Italian, Asian, European, African, German, and France populations. The frequency of TLR3 polymorphism was compared with Asians, Caucasians, Taiwanese, Caucasians and Saudi Arabians, Poland, Taiwanese, Italy, Taiwan, Estonia, Asia, and the Caucasus. The inter-population differences were observed in the distribution of TLR3 and TLR7 polymorphisms. Conclusion: The prevalence of TLR3 and TLR7 polymorphisms suggested that genotype-phenotype studies should be conducted among population to address the innate immune responses against pathogens.