PURPOSE: Nevirapine (NVP) is an anti-retroviral drug used for the treatment of HIV infection, that may cause several severe adverse events, including Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). A recent whole genome association study highlighted a strong association with allopurinol-induced SJS/TEN within the HCP5 and PSORS1C1 genes in the Japanese population. Our aim was to verify the contribution of these two genes in the susceptibility to NVP-induced SJS/TEN in a population from Mozambique. METHODS: Genotyping of PSORS1C1 rs2233945 and HCP5 rs3099844 SNPs was performed in a sample of 27 patients with SJS/TEN and 76 controls. A case-control and a haplotype analysis were performed. RESULTS: The HCP5 rs3099844 variant allele was significantly associated with the SJS/TEN susceptibility (OR = 2.03 and P = 0.039). The TA haplotype, carrying both the variant alleles of the two genes, showed a higher risk for developing SJS/TEN (OR = 3.44and P = 0.003). The regression analysis confirmed the contribution of HCP5 rs3099844 SNP (OR = 2.05, P = 0.047). By a log-linear model, we also investigated for interaction between HCP5 rs309844 and PSORS1C1 rs2233945 SNPs with respect to SJS/TEN risk, and we observed a strong interaction between the two SNPs (P = 0.005). CONCLUSIONS: We confirmed the association of HCP5 with the SJS/TEN susceptibility in a population from Mozambique treated with NVP.
PURPOSE:Nevirapine (NVP) is an anti-retroviral drug used for the treatment of HIV infection, that may cause several severe adverse events, including Stevens Johnsons Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). A recent whole genome association study highlighted a strong association with allopurinol-induced SJS/TEN within the HCP5 and PSORS1C1 genes in the Japanese population. Our aim was to verify the contribution of these two genes in the susceptibility to NVP-induced SJS/TEN in a population from Mozambique. METHODS: Genotyping of PSORS1C1rs2233945 and HCP5rs3099844 SNPs was performed in a sample of 27 patients with SJS/TEN and 76 controls. A case-control and a haplotype analysis were performed. RESULTS: The HCP5rs3099844 variant allele was significantly associated with the SJS/TEN susceptibility (OR = 2.03 and P = 0.039). The TA haplotype, carrying both the variant alleles of the two genes, showed a higher risk for developing SJS/TEN (OR = 3.44and P = 0.003). The regression analysis confirmed the contribution of HCP5rs3099844 SNP (OR = 2.05, P = 0.047). By a log-linear model, we also investigated for interaction between HCP5rs309844 and PSORS1C1rs2233945 SNPs with respect to SJS/TEN risk, and we observed a strong interaction between the two SNPs (P = 0.005). CONCLUSIONS: We confirmed the association of HCP5 with the SJS/TEN susceptibility in a population from Mozambique treated with NVP.
Authors: M Tohkin; N Kaniwa; Y Saito; E Sugiyama; K Kurose; J Nishikawa; R Hasegawa; M Aihara; K Matsunaga; M Abe; H Furuya; Y Takahashi; H Ikeda; M Muramatsu; M Ueta; C Sotozono; S Kinoshita; Z Ikezawa Journal: Pharmacogenomics J Date: 2011-09-13 Impact factor: 3.550
Authors: Daniel F Carr; Mas Chaponda; Andrea L Jorgensen; Elena Cornejo Castro; Joep J van Oosterhout; Saye H Khoo; David G Lalloo; Robert S Heyderman; Ana Alfirevic; Munir Pirmohamed Journal: Clin Infect Dis Date: 2013-01-29 Impact factor: 9.079