Genetic interaction between two VNTRs in the MAOA gene is associated with the nicotine dependence

Abstract

Nicotine dependence is an addiction to tobacco products and a global public health concern that in part would be influenced by our genetics. Smokers are reported to have reduced MAOA activity, but the results from genetic associations with this gene have been inconclusive. Two functionally relevant variable number tandem repeat (VNTR) domains, termed uVNTR and dVNTR, in the MAOA gene are well characterized transcriptional regulatory elements. In the present study, we analyzed uVNTR and dVNTR polymorphisms in the MAOA gene in the Vietnamese male population of smokers and non-smokers in order to assess the association of MAOA with the nicotine dependence measured by the Fagerström Test for Nicotine Dependence (FTND). Individual analysis of VNTRs separately identified uVNTR to be associated with the F6 question of the FTND indicating the stronger addiction to nicotine. No associations were found between the dVNTR and smoking behavior. The combination of dVNTR and uVNTR, that predicts low expression of MAOA (10–3 haplotypes), was significantly associated with the higher nicotine dependence (FTND score), longer smoking duration, and more persistent smoking behavior (fewer quit attempts). In conclusion, our study confirms that low MAOA expression is genetically predictive to the higher nicotine dependence. Impact statement The present study combined the analysis of two transcriptional regulators, uVNTR and dVNTR, in the MAOA gene that is an enzyme responsible for the monoamine degradation and identified genetic interaction between these VNTRs in association with the nicotine dependence. The main impact is that when analyzing different populations in the genetic studies, the functionally meaningful variants should be combined rather than addressing individual elements separately (a mini polygenic risk score for a particular gene/locus). This combination is very rarely analyzed and therefore the study sets an example. Another impact is that we analyzed the genetic variability in the Asian population and therefore our data present a piece of information from underrepresented populations.

Insights on the pathogenesis of type 2 diabetes as revealed by signature genomic classifiers in an African American population in the Washington, DC area

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Second-Hand Smoking Prevalence in Vietnamese Population Aged 15 and older: A Systematic Review and Meta-Analysis

“…First, the physical dependence on tobacco was shown to be common among Vietnamese adult males, despite the fact that the tobacco user had a strong desire to stop smoking. 24 And second, several studies have shown evidence of genetic impacts on nicotine dependency, for example, It is genetically predicated that Vietnamese male smokers with less MAOA expression would have greater nicotine dependency 25 and HTTLPR and STin2 VNTRs interact genetically to regulate nicotine dependence, with STin2 effects predominating. 26 It has potential benefits that an crucial step in transferring these genetic discoveries into clinical practice is discovering the genetic characteristics that influence smoking cessation in order to improve the effectiveness of existing smoking cessation therapies.…”

Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients

“…The results showed that carriers of S/S HTTLPR genotype showed a stronger association between STin2 10/10 variant and number of cigarettes smoke per day [ 42 ]. Another genetic investigation showed that the interaction between uVNTR and dVNTR in the monoamine oxidase A (MAOA) gene was significantly associated with nicotine dependence [ 43 ]. As the interaction between VNTRs within the gene may regulate its transcriptional expression, further studies are needed to estimate the role of genetic interaction between the DRD4 Exon III or 5-HTTLPR VNTR polymorphisms and other genetic markers in individual phenotype and the relation with psychiatric symptoms in HD patients.…”