CYP2B6 G516T genotyping in a UK cohort of HIV-positive patients: polymorphism frequency and influence on efavirenz discontinuation.
OBJECTIVE
The nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz undergoes phase I metabolism by the cytochrome P450 enzyme, CYP2B6. Previous studies outside of the United Kingdom have shown associations between the CYP2B6 polymorphism G516T and increased toxicity. This study aimed to develop a CYP2B6 G516T genotyping assay to identify individuals at risk of efavirenz toxicity. The frequency of this polymorphism in a UK HIV-infected population and its prevalence in individuals who had discontinued efavirenz were also to be assessed.


METHODS
Genomic DNA from HIV-positive patients (n = 206) attending clinic at Southmead Hospital, North Bristol NHS Trust was extracted from spare blood taken for CD4 monitoring. An allele-specific polymerase chain reaction (PCR) method for the CYP2B6 G516T polymorphism was used to assign patients' genotypes. Patients' age, sex, ethnicity and drug history were also recorded.


RESULTS
The G516T polymorphism was more prevalent in Blacks (16%; n = 10/63) than Caucasians (6%; n = 9/143). No significant difference in the distribution of genotypes between individuals who had discontinued efavirenz (n = 31) and individuals who had continued efavirenz (n = 74) was observed (chi(2); P = 0.63).


CONCLUSIONS
A genotyping method for the CYP2B6 G516T method was used to assess the polymorphism frequency in a UK cohort of HIV-infected patients. The polymorphism was not more prevalent in individuals who had discontinued efavirenz. Reasons for drug discontinuation are likely to be multifactorial and as this study showed cannot be explained by this genetic difference alone. For this reason we do not advocate testing for this polymorphism in routine clinical practice at present.
Powers
Vicki
V
Department of Biochemistry, University Hospitals Bristol NHS Foundation Trust, Bristol Royal Infirmary, Bristol, UK. Victoria.Powers@UHBristol.nhs.uk
Ward
J
J
Gompels
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000480:Alkynes; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000009:adverse effects*; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D006113:United Kingdom; D044465:White People / Q000235:genetics; D055815:Young Adult
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz