Year: 2008
Type: dissertation
Study design: Observational Study
Abstract: Smoking is the most common reason for preventable untimely death. Tobacco products are related to one fourth of the self-inflicted diseases. Smoking is the most important known risk factor of cancers. About 30 % of the diagnosed cancers in Finland are related to smoking. Smoking increases heart attack risk by 2-fold. According to WHO approximately five million people die due to tobacco use every year. It has been estimated that this number will increase to ten million people by 2030. Very often the closest relatives of a smoker also become smokers. Therefore, it is believed that also genetic variants are related to smoking. Tobacco consists of over 4000 different chemical compounds, but only one of these compounds, nicotine, is believed to be addictive. Family, twin and adoption studies have revealed a strong genetic component in nicotine addiction. However, surprisingly little is known about the genetics of smoking and nicotine dependence. In this candidate gene study the aim was to identify genes involved in nicotine dependence in Finnish twin families. The study sample consisted of Finnish twins and their siblings born in 1945 – 1955. They were selected based on history of heavy smoking in at least two sibs. Nicotine dependence has been evaluated from a diagnostic telephone interview using the DSM-IV criteria and the Fagerstrom score. 720 individuals were included in this study. Studied phenotypes were nicotine dependence (DSM-IV score) and regular smoker (smoker or non-smoker). The allelic spectrum of candidate genes was analyzed by using single nucleotide polymorphisms (SNPs). Six candidate genes with functional relevance were selected from the literature: four nicotinic acetylcholine receptor genes and two cytochrome P450 genes. Sequenom’s Mass ARRAY technology was utilised to genotype 26 SNPs that were selected based on their genetic location, polymorphic nature and linkage disequilibrium in Finnish families. Family based association analyses were then used to evaluate the role of specific alleles. The results show statistically significant association in three genes with nicotine dependence: CHRNA5 (rs667282, rs3743078), CHRNA4 (rs2273502, rs2273505) and CHRNB1 (rs2302763, rs871990) and two genes with regular smoker phenotype CHRNA5 (rs3743078) and CHRNB1 (rs2302767, rs2302762). These results with nicotine dependence phenotype are similar to the ones reported earlier. In short, these results show that genetic components play a role in nicotine dependence and give us more perspective in revealing them in more detail.
Author: Katri Heikkilä
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G9000243987
OpenAlex ID: W2282506433