BACKGROUND: Pharmacologic studies implicate a significant role of genes encoding the serotonin transporter (SLC6A4) and the 5-HT3AB subunits HTR3A and HTR3B in nicotine dependence (ND). However, whether they are involved in ND remains largely unknown. METHODS: Here, we examined the impact of variations in the three genes on ND in 1366 individuals from 402 African American (AA) and 671 individuals from 200 European American (EA) families. The ND of each smoker was assessed with smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström test for nicotine dependence (FTND). RESULTS: Association analysis revealed marginal association of rs10160548 in HTR3A with SQ and HSI in AA, 5-HTTLPR in SLC6A4 with FTND in EA, and rs11606194 in HTR3B with SQ and FTND in the pooled sample. Haplotype-based association analysis revealed a few major haplotypes in HTR3A that were significantly associated with ND in the AA, EA, and pooled samples. However, none of these associations remained significant after correcting for multiple testing except for a haplotype G-C-C-T-A-T formed by SNPs rs1150226, rs1062613, rs33940208, rs1985242, rs2276302, and rs10160548 in HTR3A for the AA sample. Considering biological functions of the three genes, we examined interactive effects of variants in the three genes, which revealed significant interactions among rs1062613 and rs10160548 in HTR3A, rs1176744 in HTR3B, and 5-HTTLPR and rs1042173 in SLC6A4 in affecting ND in the three samples. CONCLUSIONS: We conclude that SLC6A4, HTR3A and HTR3B play a significant role in ND through genetic interactions.
BACKGROUND: Pharmacologic studies implicate a significant role of genes encoding the serotonin transporter (SLC6A4) and the 5-HT3AB subunits HTR3A and HTR3B in nicotine dependence (ND). However, whether they are involved in ND remains largely unknown. METHODS: Here, we examined the impact of variations in the three genes on ND in 1366 individuals from 402 African American (AA) and 671 individuals from 200 European American (EA) families. The ND of each smoker was assessed with smoking quantity (SQ), heaviness of smoking index (HSI), and Fagerström test for nicotine dependence (FTND). RESULTS: Association analysis revealed marginal association of rs10160548 in HTR3A with SQ and HSI in AA, 5-HTTLPR in SLC6A4 with FTND in EA, and rs11606194 in HTR3B with SQ and FTND in the pooled sample. Haplotype-based association analysis revealed a few major haplotypes in HTR3A that were significantly associated with ND in the AA, EA, and pooled samples. However, none of these associations remained significant after correcting for multiple testing except for a haplotype G-C-C-T-A-T formed by SNPs rs1150226, rs1062613, rs33940208, rs1985242, rs2276302, and rs10160548 in HTR3A for the AA sample. Considering biological functions of the three genes, we examined interactive effects of variants in the three genes, which revealed significant interactions among rs1062613 and rs10160548 in HTR3A, rs1176744 in HTR3B, and 5-HTTLPR and rs1042173 in SLC6A4 in affecting ND in the three samples. CONCLUSIONS: We conclude that SLC6A4, HTR3A and HTR3B play a significant role in ND through genetic interactions.
Authors: S Mihailescu; M Palomero-Rivero; P Meade-Huerta; A Maza-Flores; R Drucker-Colín Journal: Eur J Pharmacol Date: 1998-10-30 Impact factor: 4.432
Authors: Matthew Randesi; Wim van den Brink; Orna Levran; Peter Blanken; Jan M van Ree; Jurg Ott; Mary Jeanne Kreek Journal: Pharmacogenomics Date: 2019-04-15 Impact factor: 2.533
Authors: Thalida E Arpawong; Jinkook Lee; Drystan F Phillips; Eileen M Crimmins; Morgan E Levine; Carol A Prescott Journal: Behav Genet Date: 2015-09-02 Impact factor: 2.805
Authors: Chamindi Seneviratne; Jason Franklin; Katherine Beckett; Jennie Z Ma; Nassima Ait-Daoud; Thomas J Payne; Bankole A Johnson; Ming D Li Journal: Hum Genet Date: 2013-06-12 Impact factor: 4.132
Authors: Jacqueline M Vink; Toos C E M van Beijsterveldt; Charlotte Huppertz; Meike Bartels; Dorret I Boomsma Journal: Addict Biol Date: 2015-01-13 Impact factor: 4.280
Authors: N A Fineberg; Z Demetrovics; D J Stein; K Ioannidis; M N Potenza; E Grünblatt; M Brand; J Billieux; L Carmi; D L King; J E Grant; M Yücel; B Dell'Osso; H J Rumpf; N Hall; E Hollander; A Goudriaan; J Menchon; J Zohar; J Burkauskas; G Martinotti; M Van Ameringen; O Corazza; S Pallanti; S R Chamberlain Journal: Eur Neuropsychopharmacol Date: 2018-10-10 Impact factor: 4.600