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Genetic interaction between Two VNTRs in the SLC6A4 gene regulates nicotine dependence in Vietnamese Men
Journal article   Open access   Peer reviewed

Genetic interaction between Two VNTRs in the SLC6A4 gene regulates nicotine dependence in Vietnamese Men

G. Kõks, E. Prans, H.D.T. Tran, N.B.T. Ngo, L.N.N. Hoang, H.M.T. Tran, T. Cao Ngoc, T. Doan Phuoc, X.D. Ho, B. Ho Duy, …
Frontiers in Pharmacology, Vol.9
2018
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Abstract

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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.21 Psychiatry
1.21.1519 Neurotransmitter Gene Variants
Web Of Science research areas
Pharmacology & Pharmacy
ESI research areas
Pharmacology & Toxicology
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