Lack of an association between SNPs within the cholinergic receptor genes and smoking behavior in a Czech post-MONICA study

Abstract

Smoking has a significant heritable component of approximately 30–60%. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) within the nicotinic cholinergic receptor subunits 3 (rs578776), 5 (rs16969968) and β3 (rs6474412), which are associated with nicotine dependence in Western European populations. To analyze the association in a Czech population, we genotyped 1,191 males and 1,368 females (post-MONICA study). The WHO protocol was used to examine smoking status and the number of cigarettes smoked per day. There were 32.1% current and 27.6% past smokers among the males and 22.5% current and 13.8% past smokers among the females. We have not confirmed the original results: the SNPs rs16969968 (p = 0.07), rs578776 (p = 0.16) and rs6474412 (p = 0.76) were not associated with smoking status (never-smokers vs. ever-smokers) in the entire population, if a codominant model of analysis was used. This result was valid for both the male and female subpopulations if analyzed separately and adjusted for age. Finally, in ever-smokers, the number of cigarettes smoked per day was also independent of different genotypes, regardless of which polymorphism (and gender) was analyzed (the lowest p value was 0.49). The association between the cholinergic receptors–nicotinic subunits (-3, -5 and -ß3), and smoking behavior may be population-dependent.

Significant association of the CHRNB3-CHRNA6 gene cluster with nicotine dependence in the Chinese Han population

“…Meanwhile, the reported largest GWAS of smoking with the African American samples did not identify this locus to be significant 26 . Given the known ethnic differences in physiological processes and behavior underlying ND 42 – 45 , 50 , it is of great interest to determine whether this gene cluster is associated with ND in smokers of other populations, especially Asians. To attack this issue, we conducted the present study designed to investigate the association of candidate genes with ND in a Chinese Han population.…”

“…Considering that nearly all subjects used in GWAS or candidate gene-based association studies were of European origin, it would be interesting to know whether SNPs in CHRNA6 and CHRNB3 are also involved in ND in smokers of other ethnicities. Given the demonstrated differences across ethnicities with respect to genetics, physiological processes, and behavior underlying ND 42 – 45 , it is necessary to conduct this kind of work with samples of other ethnicities, such as Chinese smokers, as we report in this study.…”

SNPs within CHRNA5-A3-B4 and CYP2A6/B6, nicotine metabolite concentrations and nicotine dependence treatment success in smokers

“…DNA was isolated from frozen EDTA blood using a standard "salting-out" method 19 . Three variants (rs16969968, rs6474412 and rs578776) were genotyped using PCR-RFLP, as described in detail previously 20 . The remaining two variants (rs4105144 and rs3733829) were analysed using TaqMan assays (C43815914 and C 2883084 1) on the 7300 Real-Time PCR System 10 .…”

MRAS gene marker rs9818870 is not associated with acute coronary syndrome in the Czech population and does not predict mortality in males after acute coronary syndrome

“…These individuals were selected according to the WHO MONICA Project protocol as a 1% general population sample from 9 different Czech districts. 15,16 Mortality data (3-8 years after ACS) for males was obtained from the Institute of Health Information and Statistics (under the Ministry of Health of the Czech Republic), where all death certificates of the Czech population are registered and analyzed. In our study we analyzed "all-cause mortality" and "cardiovascular mortality".…”