NDLI: A Common Haplotype of the Nicotine Acetylcholine Receptor α4 Subunit Gene Is Associated with Vulnerability to Nicotine Addiction in Men

Content Provider	PubMed Central
Author	Feng, Yan Niu, Tianhua Xing, Houxun Xu, Xin Chen, Changzhong Peng, Shaojie Wang, Lihua Laird, Nan Xu, Xiping
Copyright Year	2004
Abstract	Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait ( Z=-3.04, P<.005) and significant decreases of age-adjusted FTND ( Z=-3.31, P<.005) or RTQ scores ( Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.
Related Links	http://dx.doi.org/10.1086/422194
Ending Page	121
Page Count	10
Starting Page	112
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	1
Volume Number	75
Language	English
Publisher	The American Society of Human Genetics
Publisher Date	2004-07-01
Access Restriction	Open
Rights Holder	The American Society of Human Genetics
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men.

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