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Prevalence and correlates of CYP2B6-G516T polymorphisms in a cohort of HIV-infected women and children in Canada
Abstract Content:
Background: The G516T polymorphism within the CYP2B6-gene
affects the metabolism of non-nucleoside reverse transcriptase inhibitors
(NNRTIs), with rapid NNRTI metabolism among homozygous GG individuals, and slow
metabolism among those with TT genotype.
The objective of this study was to describe the prevalence of the G516T genotypes
among a cohort of HIV infected women and children in Canada, and associated
clinical correlates.
Methods: HIV infected women and children were recruited from the Centre Maternel et Infantil sur le SIDA (CMIS) mother-child cohort between 2013-2014; family members were excluded from the study. DNA was extracted from saliva samples, and genotyping was performed using CYP2B6-G516T specific amplification and restriction fragment length polymorphism (PCR-RFLP).
Results: Genotyping was performed on 89 subjects (46 women, 43 children). Self-described ethnic distribution was African (46.1%), Haitian (31.5%), Caucasian (12.4%), and mixed origin (10%). Overall, 38.2% were GG (rapid metabolizers), 49.4% were GT , and 12.4% were TT (slow metabolizers). Among Africans, the GG genotype was most prevalent (46.3%), followed by GT (41.4%) and TT (12.2%). Among Haitians, the GT genotype was most prevalent (64.3%), followed by GG (21.4%) and TT (14.3%). Among Caucasians, 54.5% were GG, 36.4% were GT, and 9.1% were TT. There was a significant difference in the proportion of rapid metabolizers (GG) between Africans and Haitians (46.3% vs 21.4%, p=0.04), with an equal distribution of the GG genotype between patients from West Africa (43%) and Sub-Saharan Africa (44%). The highest proportion of slow metabolizers (TT) was among West Africans (21.5%), while the highest proportion of rapid metabolizers was among European Caucasians (75%). Among children treated with standard (weight/kg) doses of Efavirenz for whom unadjusted drug levels were available, 4/6 (67%) of GG genotype had trough drug levels in the lower therapeutic range (1-2 mg/L) at steady state, as compared to only 3/8 (38%) among the GT genotype. The single child with TT genotype had supra-therapeutic levels (>10mg/L) on standard dosing.
Conclusions: In this study population, the heterozygous GT genotype dominated, though there were significant differences within the predominant ethnic groups represented. Population-based knowledge of these genotypes may help tailor standard NNRTI dosing regimens to optimize their efficacy.
Methods: HIV infected women and children were recruited from the Centre Maternel et Infantil sur le SIDA (CMIS) mother-child cohort between 2013-2014; family members were excluded from the study. DNA was extracted from saliva samples, and genotyping was performed using CYP2B6-G516T specific amplification and restriction fragment length polymorphism (PCR-RFLP).
Results: Genotyping was performed on 89 subjects (46 women, 43 children). Self-described ethnic distribution was African (46.1%), Haitian (31.5%), Caucasian (12.4%), and mixed origin (10%). Overall, 38.2% were GG (rapid metabolizers), 49.4% were GT , and 12.4% were TT (slow metabolizers). Among Africans, the GG genotype was most prevalent (46.3%), followed by GT (41.4%) and TT (12.2%). Among Haitians, the GT genotype was most prevalent (64.3%), followed by GG (21.4%) and TT (14.3%). Among Caucasians, 54.5% were GG, 36.4% were GT, and 9.1% were TT. There was a significant difference in the proportion of rapid metabolizers (GG) between Africans and Haitians (46.3% vs 21.4%, p=0.04), with an equal distribution of the GG genotype between patients from West Africa (43%) and Sub-Saharan Africa (44%). The highest proportion of slow metabolizers (TT) was among West Africans (21.5%), while the highest proportion of rapid metabolizers was among European Caucasians (75%). Among children treated with standard (weight/kg) doses of Efavirenz for whom unadjusted drug levels were available, 4/6 (67%) of GG genotype had trough drug levels in the lower therapeutic range (1-2 mg/L) at steady state, as compared to only 3/8 (38%) among the GT genotype. The single child with TT genotype had supra-therapeutic levels (>10mg/L) on standard dosing.
Conclusions: In this study population, the heterozygous GT genotype dominated, though there were significant differences within the predominant ethnic groups represented. Population-based knowledge of these genotypes may help tailor standard NNRTI dosing regimens to optimize their efficacy.