Nicotine dependence is an addiction to tobacco products and a global public health concern. Association between the SLC6A4 polymorphisms and nicotine dependence is controversial. Two variable number tandem repeat (VNTR) domains, termed HTTLPR and STin2, in the SLC6A4 gene are well characterized transcriptional regulatory elements. Their polymorphism in the copy number of the repeat correlates with the particular personality and psychiatric traits. We analyzed nicotine dependence in 1,804 participants from Central Vietnam. The Fagerström Test (FTND) was used to evaluate the nicotine dependence and PCR was used to determine the SLC6A4 HTTLPR and STin2 VNTRs. The HTTLPR VNTR was associated with difficulties to refrain from smoking in a prohibiting environment. The STIn2 10/10 genotype was associated with (1) years of smoking, (2) difficulties to quit the first cigarette, and (3) higher number of cigarettes smoked per day (CPD). Stratification analysis was used to find the genetic interaction between these two VNTRs in nicotine dependence as they may synergistically regulate the SLC6A4 expression. Smokers with the S/S HTTLPR genotypes showed a much stronger association between STin2 10/10 variant and CPD. This finding is consistent with the molecular evidence for the functional interaction between HTTLPR and STin2 in cell line models, where STin2 has described as a stronger expressional regulator. Similarly, we found that STin2 is a much stronger modifier of smoking with 10/10 genotype related to higher nicotine dependence. The present study supports genetic interaction between HTTLPR and STin2 VNTRs in the regulation of nicotine dependence with the dominance of the STin2 effects. This finding could be explained by their differential effect on the SLC6A4 expression.

Tobacco is legally permitted for adults, easily available, and the prevalence of smoking is high. Tobacco use is the largest preventable risk factor for human disease. To reduce smoking, many countries have introduced public policy to restrict the distribution of tobacco. The aim of this study was to analyse tobacco smoking and nicotine dependence in Central Vietnamese men around Hue and Da Nang cities. Nicotine dependence was measured using the Fagerström Test for Nicotine Dependence (FTND) score. The cohort contained total of 1822 Central Vietnamese men from Hue and Da Nang: 1453 smokers and 369 non-smokers. Individuals completed a questionnaire and factors such as smoking initiation, quitting behaviour, and success in quitting were also recorded. In the smoking group, the average amount of time in which the individual had smoked was 26.4 years. Average FTND value was 4.02, median was 4, the first quartile was 2, and the third quartile was 6. In all, 431 smokers (30%) had an FTND score of 6 or higher; an FTND score of this value is considered to equate to an individual having high nicotine dependence. Therefore, it could be noted that high nicotine dependence is very common in Central Vietnam. High nicotine dependence was significantly correlated with years of smoking. The longer the smoking period, the higher the FTND score. A high FTND score correlated with the individual being less likely to successfully quit smoking. The results of the questionnaire demonstrate that even when there is no restriction in public policy concerning the distribution of tobacco, individuals still wish to quit smoking. This study identified a high prevalence of severe nicotine dependence in Central Vietnamese men and the majority smokers wished to quit smoking. Consequently, the results of this study highlight the acute need for a specific programme to aid smokers in Central Vietnam to quit smoking.