Association between genetic variants on chromosome 15q25 locus and several nicotine dependence traits in Polish population: a case-control study.

Krzysztof Buczkowski,Alicja Sieminska,Grzegorz Przybylski,Tomasz Grzybowski,Slawomir Czachowski,Katarzyna Linkowska,Ewa Jassem

doi:10.1155/2015/350348

Abstract

Tobacco smoking continues to be a leading cause of disease and mortality. Recent research has confirmed the important role of nicotinic acetylcholine receptor (nAChR) gene cluster on chromosome 15q 24-25 in nicotine dependence and smoking. In this study we tested the association of smoking initiation, age at onset of daily smoking, and heaviness of smoking with five single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster. The group of 389 adult subjects of European ancestry from the north of Poland, including 212 ever (140 current and 72 former) and 177 never smokers with mean age 49.26, was genotyped for rs16969868, rs1051730, rs588765, rs6495308, and rs578776 polymorphisms. Distributions of genotypes for rs16969868 and rs1051730 were identical so they were analyzed together. Further analysis revealed the association between rs16969868-1051730 (OR = 2.66; 95% CI: 1.30–5.42) and number of cigarettes smoked per day (CPD) with heaviness of nicotine addiction measured by the Fagerström Test for Nicotine Dependence (FTND) (OR = 2.60; 95% CI: 1.24–5.43). No association between these polymorphisms and other phenotypes was found. Similarly, the association between rs588765, rs6495308, rs578776, and analyzed phenotypes was not confirmed. This study provides strong evidence for the role of the CHRNA5-CHRNA3-CHRNB4 cluster in heaviness of nicotine addiction.

Highlights

Tobacco smoking is a serious public health concern responsible for approximately 5 million deaths a year [1] and is an important risk factor for 21% of cancers [2] and by the year 2015 is projected to be responsible for 10% of all deaths globally [1].Evidence from twin studies proved genetic influences on nicotine dependence (ND) [3] and gave impulse to the search for genetic variants that influence ND
BioMed Research International smoking [7], cigarettes per day (CPD) [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20], ND defined by the Fagerstrom Test for Nicotine Dependence (FTND) [4, 5, 7, 11, 14, 21,22,23,24,25,26,27,28,29], and age at smoking initiation [27, 30, 31]
Distributions of genotypes for rs16969868, rs1051730, rs588765, rs6495308, and rs578776 polymorphisms did not deviate to any appreciable extent from expectations predicted by the HardyWeinberg equilibrium as determined by Arlequin v.3.1 software (P = 0.8172, P = 0.8172, P = 0.5442, P = 0.6455, and P = 0.5946, resp.)

Summary

Introduction

Evidence from twin studies proved genetic influences on nicotine dependence (ND) [3] and gave impulse to the search for genetic variants that influence ND. This more recent molecular approach indicates that smoking-related phenotypes are highly heritable [4,5,6]. In previous years genome-wide association studies and some meta-analyses have reported associations between single nucleotide polymorphisms (SNPs) in the CHRNA5CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) gene cluster on chromosome 15q 24-25 and some phenotypes describing smoking behavior like ever. Nicotine, which is a naturally occurring alkaloid in tobacco, affects the body mainly through its influence on nAChRs, for which the natural ligand is acetylcholine [34, 35]

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