Rs1051730

rs1051730, also known as D398N, is a SNP in the nicotinic acetylcholine receptor alpha 3 subunit CHRNA3 gene.

In two recent (2008) studies, together comprising over 6,000 lung cancer patients of European ancestry, the rs1051730(T) allele was very significantly associated with increased risk. Having one copy (i.e. being a rs1051730(C;T) genotype) increased risk for lung cancer about 1.3x, and having two copies (rs1051730(T;T) individuals) represented 1.8x increased risk. Up to 14% of lung cancer incidence may be attributable to this allele.[PMID 18385738, PMID 18385676]

An independent study published at the same time concluded that (T) allele carriers for SNP rs1051730 are not at higher risk of becoming smokers compared to (C) carriers. However, if they do smoke, (T) carriers are quite likely to smoke more cigarettes than (C) carriers, and as an apparent consequence, they are at higher risk for lung cancer as reported in this and other studies. This study therefore links rs1051730 directly to nicotine dependence, and indirectly to lung cancer. [PMID 18385739]

According to DeCODE, the CC genotype at rs1051730 is associated with 0.88x risk of peripheral arterial disease (PAD). [PMID 18385739]

Note: publications tend to refer to the risk allele as "A", however, the orientation reported for rs1051730 in dbSNP is for the opposite strand, so in keeping with reporting all SNPs in the orientation published in dbSNP, SNPedia refers to this same risk allele as the (T) allele.

spittoon (T;T) once more smoke per day.

[PMID 19064933] rs1051730 influences how much alcohol it takes to have you feel a buzz. More professorially: rs1051730 influences the level of response to alcohol intake, as measured by body sway after having a 10am "3 drink challenge". rs1051730(T;T) individuals respond slower to alcohol, which generally is considered to actually increase their long-term risk of alcohol abuse.

spittoon (T;T) makes it harder to quit smoking

GWAS
SNP	rs1051730
PubMedID	[PMID 18385739]
Condition	Nicotine dependence
Gene	CHRNA3,CHRNA5,CHRNB4
Risk Allele	T
pValue	6.00E-020
OR	0.1
95% CI	0.08-0.12) increase in cigarettes per da

[PMID 19247474] Genome-wide and candidate gene association study of cigarette smoking behaviors.

[PMID 19300482] A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci.

GWAS snp
PMID	[PMID 18978790]
Trait	Lung cancer
Title	Lung cancer susceptibility locus at 5p15.33
Risk Allele	A
P-val	1E-15
Odds Ratio	1.35 [1.25-1.45]

[PMID 19465454] The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung

[PMID 19641473] Racial Differences in the Association Between SNPs on 15q25.1, Smoking Behavior, and Risk of Non-small Cell Lung Cancer

[PMID 19733931] Blood-based CHRNA3 single nucleotide polymorphism and outcome in advanced non-small-cell lung cancer patients

GWAS snp
PMID	[PMID 19836008]
Trait	Lung adenocarcinoma
Title	A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma
Risk Allele	T
P-val	2E-51
Odds Ratio	1.31 [1.27-1.36]

[PMID 19132693] Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence

[PMID 20068085] Analysis of Genetic Variants in Never-Smokers with Lung Cancer Facilitated by an Internet-Based Blood Collection Protocol: A Preliminary Report

[PMID 20418890] Genome-wide meta-analyses identify multiple loci associated with smoking behavior

GWAS snp
PMID	[PMID 20418889]
Trait	Smoking behavior
Title	Meta-analysis and imputation refines the association of 15q25 with smoking quantity
Risk Allele	G
P-val	2E-66
Odds Ratio	0.08 [0.07-0.09] unit decrease

GWAS snp
PMID	[PMID 20418888]
Trait	Smoking behavior
Title	Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
Risk Allele	A
P-val	2E-69
Odds Ratio	0.80 [0.70-0.90] CPD increase

[PMID 20554942] Nicotinic Acetylcholine Receptor Region on Chromosome 15q25 and Lung Cancer Risk Among African Americans: A Case-Control Study

[PMID 20564069] Mediating effects of smoking and chronic obstructive pulmonary disease on the relation between the CHRNA5-A3 genetic locus and lung cancer risk

[PMID 20393456] Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers

[PMID 21248747] Association of a variant in the CHRNA5-A3-B4 gene cluster region to heavy smoking in the Italian population

[PMID 21511889] Variant Within the Promoter Region of the CHRNA3 Gene Associated With FTN Dependence Is Not Related to Self-reported Willingness to Quit Smoking

[PMID 21646606] Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study

[PMID 21645942] Association of smoking with tumor size at diagnosis in non-small cell lung cancer

[PMID 21685187] Genome-wide association study of smoking behaviours in patients with COPD

[PMID 21858091] In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression

[PMID 22441734] CHRNA3 genotype, nicotine dependence, lung function and disease in the general population