CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women

David N. Feldman, Joseph G. Feldman, Ruth Greenblatt, Kathryn Anastos, Leigh Pearce, Mardge Cohen, Stephen J Gange, Suzanne Leanza, Robbie Burk

Research output: Contribution to journalArticle

Abstract

We have recently shown that cigarette smoking is associated with lesser responses to potent antiretroviral therapies. Certain Cytochrome P-450 enzymes activate compounds derived from tobacco smoke into toxic forms that may promote HIV-1 gene expression through promotion of DNAadduct formation by the oxidation of chemical constituents of cigarette smoke, such as polyaromatic hydrocarbons and dioxins. To explore the association between environmental and genetic factors to viral replication in women who smoke and receive highly active anti-retroviral therapy (HAART), we assessed the impact of polymorphisms in a panel of four Cytochrome P-450 genes (CYP1A1, CYP2A6, CYP2D6, and CYP2E1) and two Glutathione S-transferase genes (GSTM1 and GSST1) in 924 participants of the Women's Interagency HIV Study (WIHS). Our findings showed that GSTM1 and GSST1 deletions were not associated with HAART effectiveness. By contrast, homozygosity for the CYP1A1-m1 polymorphism, was associated with impaired viral response to treatment among smokers (relative hazard (RH) = 0.54; 95% confidence interval = 0.31-0.94) after adjustment for pretreament viral load, CD4 count, age, hepatitis C infection, prior HAART therapy and race, although it had no effect among nonsmokers. We conclude that the association of the CPY1A1-m1 variant with a reduced response to HAART therapy in HIV infected smokers is consistent with this enzyme's role in the metabolic conversion of environmental toxins to DNA adducts, which may directly promote HIV-1 gene expression.

Original languageEnglish (US)
Pages (from-to)81-93
Number of pages13
JournalAIDS Education and Prevention
Volume21
Issue numberSUPPL. 3
DOIs
StatePublished - Jun 2009

Fingerprint

Cytochrome P-450 CYP1A1
smoking
Smoking
Genotype
Smoke
Therapeutics
HIV-1
HIV
heredity
Gene Expression
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP2D6
Dioxins
DNA Adducts
Poisons
CD4 Lymphocyte Count
Hepatitis C
nicotine
Hydrocarbons
contagious disease

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases
  • Health(social science)
  • Medicine(all)

Cite this

Feldman, D. N., Feldman, J. G., Greenblatt, R., Anastos, K., Pearce, L., Cohen, M., ... Burk, R. (2009). CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. AIDS Education and Prevention, 21(SUPPL. 3), 81-93. https://doi.org/10.1521/aeap.2009.21.3_supp.81

CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. / Feldman, David N.; Feldman, Joseph G.; Greenblatt, Ruth; Anastos, Kathryn; Pearce, Leigh; Cohen, Mardge; Gange, Stephen J; Leanza, Suzanne; Burk, Robbie.

In: AIDS Education and Prevention, Vol. 21, No. SUPPL. 3, 06.2009, p. 81-93.

Research output: Contribution to journalArticle

Feldman, DN, Feldman, JG, Greenblatt, R, Anastos, K, Pearce, L, Cohen, M, Gange, SJ, Leanza, S & Burk, R 2009, 'CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women', AIDS Education and Prevention, vol. 21, no. SUPPL. 3, pp. 81-93. https://doi.org/10.1521/aeap.2009.21.3_supp.81
Feldman DN, Feldman JG, Greenblatt R, Anastos K, Pearce L, Cohen M et al. CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. AIDS Education and Prevention. 2009 Jun;21(SUPPL. 3):81-93. https://doi.org/10.1521/aeap.2009.21.3_supp.81
Feldman, David N. ; Feldman, Joseph G. ; Greenblatt, Ruth ; Anastos, Kathryn ; Pearce, Leigh ; Cohen, Mardge ; Gange, Stephen J ; Leanza, Suzanne ; Burk, Robbie. / CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. In: AIDS Education and Prevention. 2009 ; Vol. 21, No. SUPPL. 3. pp. 81-93.
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