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CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents

CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents
CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents
Objectives: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents.
Methods: 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years.
Results: No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR=2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR=1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups.
Conclusions: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.
1744-6872
839-850
Huang, Shuwen
50d7f3f2-2767-462c-a3f9-bf4711657e1f
Cook, Derek G.
0e13cfdc-c3f8-4f3f-834a-858c2a0c34cc
Hinks, Lesley J.
26543550-2e57-4947-9737-25c4c4ab1163
Chen, Xiao-he
fd93b896-d8cc-4b0e-a811-c0e6a8ff8308
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Gilg, Julie A.
35ef73ff-a947-4dcf-a94b-93f1909a64ac
Jarvis, Martin J.
04dbbdd2-8f3c-4346-b04c-81c2f6f391a6
Whincup, Peter H.
b2f4a9dd-9b42-4f44-b078-575d5d9da0dc
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Huang, Shuwen
50d7f3f2-2767-462c-a3f9-bf4711657e1f
Cook, Derek G.
0e13cfdc-c3f8-4f3f-834a-858c2a0c34cc
Hinks, Lesley J.
26543550-2e57-4947-9737-25c4c4ab1163
Chen, Xiao-he
fd93b896-d8cc-4b0e-a811-c0e6a8ff8308
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Gilg, Julie A.
35ef73ff-a947-4dcf-a94b-93f1909a64ac
Jarvis, Martin J.
04dbbdd2-8f3c-4346-b04c-81c2f6f391a6
Whincup, Peter H.
b2f4a9dd-9b42-4f44-b078-575d5d9da0dc
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39

Huang, Shuwen, Cook, Derek G., Hinks, Lesley J., Chen, Xiao-he, Ye, Shu, Gilg, Julie A., Jarvis, Martin J., Whincup, Peter H. and Day, Ian N.M. (2005) CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents. Pharmacogenetics and Genomics, 15 (12), 839-850.

Record type: Article

Abstract

Objectives: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents.
Methods: 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years.
Results: No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR=2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR=1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups.
Conclusions: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.

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Published date: December 2005

Identifiers

Local EPrints ID: 24773
URI: http://eprints.soton.ac.uk/id/eprint/24773
ISSN: 1744-6872
PURE UUID: f58a8be0-f09a-47e7-98b2-d50e87e320c8

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Date deposited: 03 Apr 2006
Last modified: 22 Jul 2022 20:29

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Contributors

Author: Shuwen Huang
Author: Derek G. Cook
Author: Lesley J. Hinks
Author: Xiao-he Chen
Author: Shu Ye
Author: Julie A. Gilg
Author: Martin J. Jarvis
Author: Peter H. Whincup
Author: Ian N.M. Day

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