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A C17T polymorphism in the mu opiate receptor is associated with quantitative measures of drug use in African American women.

ABSTRACT: Previous studies of the association of the C17T polymorphism of the mu opiate receptor gene with substance dependence compared cases with substance dependence to controls and usually found no significant association. However, the studies were limited by small sample size-no study had more than 12 subjects with the TT genotype, a genotype that is rare in white and Asian subjects. Moreover, drug use is not dichotomous but follows a spectrum from non-use to modest, intermittent use, to use several times daily. We asked whether the Kreek-McHugh-Schluger-Kellogg (KMSK) scales for alcohol, cocaine, opiates and tobacco that quantify substance use during the time of a subject's maximal use might be more sensitive measures than dichotomous outcomes. We administered the KMSK scales and completed C17T genotyping on 1009 human immunodeficiency virus (HIV)-infected and 469 HIV-uninfected women in The Women's Interagency HIV Study, an ongoing study of HIV in women. Forty-two of the 697 African American, 1 of the 182 Hispanic and none of the 161 white women had the TT genotype. KMSK cocaine, alcohol and tobacco scores were significantly higher in the African American women with the TT genotype (P = 0.008, 0.0001, and 0.006, respectively), but opiate scores were not. Ordinal regression models controlling for HIV serostatus, age, education, and income had odds ratios for the TT genotype for predicting alcohol, tobacco, cocaine and opiates scores of 2.1 (P = 0.02), 2.4 (P = 0.0004), 2.0 (P = 0.03) and 1.9 (P = 0.07). We conclude that the TT genotype of OPRM1 may increase the risk of substance use and abuse.

SUBMITTER: Crystal HA

PROVIDER: S-EPMC3117061 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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A C17T polymorphism in the mu opiate receptor is associated with quantitative measures of drug use in African American women.

Crystal Howard A HA Hamon Sara S Randesi Matthew M Cook Judith J Anastos Kathryn K Lazar Jason J Liu Chenglong C Pearce Leigh L Golub Elizabeth E Valcour Victor V Weber Kathleen M KM Holman Susan S Ho Ann A Kreek Mary Jeanne MJ

Addiction biology 20101111 1

Previous studies of the association of the C17T polymorphism of the mu opiate receptor gene with substance dependence compared cases with substance dependence to controls and usually found no significant association. However, the studies were limited by small sample size-no study had more than 12 subjects with the TT genotype, a genotype that is rare in white and Asian subjects. Moreover, drug use is not dichotomous but follows a spectrum from non-use to modest, intermittent use, to use several ...[more]

PMID: 21070507

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Project description:Previous research shows that educational attainment is a protective factor for substance use and sexual risk among adolescents and young adults. Evidence also shows that this relationship may differ by race/ethnicity and gender. This study aimed to elucidate the relationship between educational attainment, substance use and sexual risk among African American women in emerging adulthood. This study uses cross-sectional data from 646 African American women (aged 18 to 25) enrolled in a randomized trial of a behavioral HIV risk-reduction intervention. At enrollment, participants completed a risk behavior assessment via audio-computer assisted self-interview and provided a urine sample for drug screening. Bivariate logistic regression analyses were conducted to examine substance use and sexual risk factors associated with educational attainment: completing some college or more vs. completing high school or less). Participants who completed some college or more (52%) were more likely to report heavy alcohol use (four or more drinks in one day) in the past 30 days (OR=1.48; p=0.014) and more likely to report alcohol or other drug use just before or during last sex (OR=1.43; p=0.026) compared with participants who completed high school or less. Completing some college or more was protective for having a positive urine screen for cocaine (OR=0.43; p=0.018) and reporting condomless sex at last sex (OR=0.71; p=0.041). Differences in positive marijuana screens, reporting a previous STI, or reporting their partner used alcohol or other drugs at last sex were not statistically significant. The findings reveal notable differences in the magnitude and direction of associations between educational attainment and substance use and sexual risk. Although educational attainment is subject to change because of the frequent pursuit of education during emerging adulthood, the findings may have important implications for tailoring HIV risk-reduction interventions to key populations, such as African American women.

Project description:BackgroundTiming of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking.ObjectivesWe assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production.MethodsA candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1β production was quantified. Medical record review determined timing of birth.ResultsWomen with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1β production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05).DiscussionWomen with GG genotype may be at risk for earlier birth because of diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

Dataset Information

A C17T polymorphism in the mu opiate receptor is associated with quantitative measures of drug use in African American women.

Publications

A C17T polymorphism in the mu opiate receptor is associated with quantitative measures of drug use in African American women.

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