TY - JOUR
T1 - SLC6A3 and body mass index in the prostate, lung, colorectal and ovarian cancer screening trial
AU - Azzato, Elizabeth M.
AU - Morton, Lindsay M.
AU - Bergen, Andrew W.
AU - Wang, Sophia S.
AU - Chatterjee, Nilanjan
AU - Kvale, Paul
AU - Yeager, Meredith
AU - Hayes, Richard B.
AU - Chanock, Stephen J.
AU - Caporaso, Neil E.
N1 - Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. EMA was funded through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc) and is currently funded through the NCI and the NIH/University of Cambridge Graduate Partnership Program. AWB was supported by the Intramural Research Program of the National Cancer Institute and is supported by U01 DA020830.
PY - 2009/1/30
Y1 - 2009/1/30
N2 - Background: To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Methods: Four polymorphisms (rs6350, rs6413429, rs6347 and the 3′ variable number of tandem repeat (3′ VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or ≥ 30 kg/m2, respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression. Results: Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, ptrend = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9). Conclusion: Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.
AB - Background: To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Methods: Four polymorphisms (rs6350, rs6413429, rs6347 and the 3′ variable number of tandem repeat (3′ VNTR) polymorphism) at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5-24.9, 25.0-29.9, or ≥ 30 kg/m2, respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression. Results: Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, ptrend = 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65-0.99, p = 0.04) and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49-0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9). Conclusion: Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.
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U2 - 10.1186/1471-2350-10-9
DO - 10.1186/1471-2350-10-9
M3 - Article
C2 - 19183461
AN - SCOPUS:60049091289
SN - 1471-2350
VL - 10
JO - BMC medical genetics
JF - BMC medical genetics
M1 - 9
ER -