Lack of Association of Alcohol Dependence and Habitual Smoking With Catechol‐O‐methyltransferase

Foroud, Tatiana; Wetherill, Leah; Dick, Danielle M.; Hesselbrock, Victor; Nürnberger, John I.; Kramer, John; Tischfield, Jay A.; Schuckit, Marc A.; Bierut, Laura J.; Xuei, Xiaoling; Edenberg, Howard J.

doi:10.1111/j.1530-0277.2007.00505.x

Cited by 45 publications

(21 citation statements)

References 67 publications

(69 reference statements)

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“…Met158 has been reported to be associated with low activity of enzyme [29,44,45] and literature suggests Asian population in which risk appears to be associated with Met158 [11,29]. Studies by Foroud et al and Ishiguro et al did not find any association with AD [10,46]. We observed significant difference between Val/Met genotype between the cases and controls.…”

Section: Discussioncontrasting

confidence: 41%

“…Contrasting results were observed by Ishiguro et al [10] who also utilized PCR-RFLP but reported no difference in allele frequency distribution between 175 cases and 354 age and sex matched Japanese subjects. A family based association study by Foroud et al [46] indicated that presence of COMT (Val158Met) polymorphism did not affect the pathology of alcohol consumption and smoking in European-Americans. Thus, irrespective of the differences in the methodology, the contradictory findings are likely due to differences in ethnicity, type of study (case-control/ family based association study) demographic differences, etc.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous genetic association studies have been conducted to determine polymorphisms in genes of the dopamine pathway [2,[38][39][40][41][42][43][44][45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

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An Association Study of the COMT and GABA Gene Variants with Alcohol Dependence

Singh¹,

Grover²,

Gupta³

et al. 2017

J Addict Res Ther

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Alcohol dependence (AD), associated with high mortality and morbidity is caused due to involvement of both environmental and genetic factors. Behavioral effects of alcohol including cognitive impairment, motor incoordination, tolerance and dependence are likely due to its effect on the multiple brain proteins including neurotransmitters. Dysfunction in these neurotransmitter systems may be at the level of enzymes involved in metabolic degradation, or receptors involved in neurotransmission like dopamine, Gamma-amino butyric acid (GABA), serotonin etc. Genetic polymorphisms in these neurotransmitter systems are implicated in conferring susceptibility to AD. Aim:To identify association of single nucleotide polymorphisms (SNPs) in COMT (rs4680 and rs2075507) and GABAA receptor genes (rs13172914 and rs211014) with AD.Method: A total of 100 AD patients diagnosed on the basis of DSM IV criteria from the outpatient clinic of the National Drug Dependence Treatment Centre (NDDTC) of All India Institute of Medical Sciences (AIIMS), and 100 healthy individuals from the general population were recruited. A detailed history including pattern of drug use and demographic details with pedigree information was noted. Genomic DNA from peripheral blood samples was processed for PCR amplification followed by restriction digestion to screen for the presence of polymorphisms. Genotype and allele frequencies were evaluated and correlated with alcohol use parameters including duration of alcohol use, age at onset of alcohol use, quantity of alcohol consumed (gms/day) and WHO ASSIST score and levels of liver function enzymes (SGPT and SGOT). Statistical analysis was performed using SPSS v21.0.Results: Genetic analysis of the study group revealed COMT rs4680 to be significantly associated with AD (p=0.03), while the other COMT SNP rs2075507 showed an association with increased levels of SGPT in the patients. GABAA receptor gene polymorphisms showed no association with AD. Conclusion:The study suggests a role of COMT gene polymorphism rs4680 in conferring susceptibility to AD.

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Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 99%

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An Association Study of the COMT and GABA Gene Variants with Alcohol Dependence

Singh¹,

Grover²,

Gupta³

et al. 2017

J Addict Res Ther

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“…For example, genetic variations in the dopamine-metabolizing enzymes catechol-O-methyltransferase and monoamine oxidase A (MAOA) have been found to be associated with the risk for alcohol dependence [75,76,77], although these results could not be uniformly replicated [78,79,80]. Other studies have linked genetic variations in the dopamine transporter 1 gene to the severity of withdrawal symptoms [81,82].…”

Section: Candidate Gene Studiesmentioning

confidence: 92%

Genetics of Alcohol Dependence: A Review of Clinical Studies

Samochowiec

Puls

et al. 2014

Neuropsychobiology

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Background/Aims: Alcohol dependence is a common severe psychiatric disorder with a multifactorial etiology. Since the completion of the human genome project and with the increased availability of high-throughput genotyping, multiple genetic risk factors for substance-related disorders, including alcohol dependence, have been identified, but not all results could be replicated. Methods: We systematically review the clinical literature on genetic risk factors for alcohol dependence and alcohol-related phenotypes, including candidate gene-based studies, linkage studies and genome-wide association studies (GWAS). Results: Irrespectively of the methodology employed, the most robust findings regarding genetic risk factors for alcohol dependence concern genetic variations that affect alcohol metabolism. GWAS confirm the importance of the alcohol dehydrogenase gene cluster on chromosome 4 in the genetic risk for alcohol dependence with multiple variants that exert a small, but cumulative influence. A single variant with strong influence on individual risk is the aldehyde dehydrogenase 2 ALDHD2*2 variant common in Asian populations. Other robust associations have been found with previously uncharacterized genes like KIAA0040, and such observations can lead to the identification of thus far unknown signaling pathways. Converging evidence also points to a role of glutamatergic, dopaminergic and serotonergic neurotransmitter signaling in the risk for alcohol dependence, but effects are small, and gene-environment interactions further increase the complexity. Conclusion: With few exceptions like ALDH2*2, the contribution of individual genetic variants to the risk for alcohol-related disorders is small. However, the concentration of risk variants within neurotransmitter signaling pathways may help to deepen our understanding of the underlying pathophysiology and thereby contribute to develop novel therapeutic strategies.

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“…The available evidence from the genetic association studies published to date on the association between alcoholism and COMT 472G/A gene polymorphism have produced inconclusive or contradicted results (Enoch et al, 2006;Foroud et al, 2007). Each of these studies typically involved few cases and controls and, therefore, was neither adequate nor sufficiently informative to clearly show an association.…”

Section: Introductionmentioning

confidence: 96%