Activation of the mesolimbic dopamine pathway appears to promote drug-and alcohol-seeking behavior in laboratory animals. Results for association and linkage analysis between various alcohol dependence phenotypes and the dopamine receptors have been quite mixed. Similarly, both positive and negative
Linkage studies of D2 and D4 receptor genes and alcoholism
β Scribed by Hill, Shirley Y.; Zezza, Nick; Wipprecht, Ginger; Xu, Jie; Neiswanger, Kathy
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 33 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0148-7299
- DOI
- 10.1002/(sici)1096-8628(19991215)88:6<676::aid-ajmg18>3.0.co;2-s
No coin nor oath required. For personal study only.
β¦ Synopsis
The purpose of the present study was to evaluate two polymorphisms near the D2 receptor gene (TaqI A RFLP and C microsatellite) and a VNTR for D4. A nonparametric linkage (NPL) technique, SIBPAL, was used to test for the presence or absence of linkage in 54 multiplex alcoholic families. These families had been ascertained through two alcoholic proband siblings in order to increase the density of alcoholic cases within these pedigrees. Phenotypic definitions of alcoholism were manipulated in an effort to determine the impact of severity (signs of physical dependence, early age of onset, presence of antisocial personality disorder) on the likelihood of finding positive evidence for linkage. A regression analysis that simultaneously evaluated the allele sharing identical by descent for Feighner criteria alcoholism in affected, unaffected, and discordant sib pairs (SIBPAL) for two D2 polymorphisms and the D4 polymorphism gave no evidence for linkage. Phenotypes associated with greater alcoholism severity (presence of physical dependence symptoms, earlier onset, or comorbid antisocial personality disorder) revealed some evidence for linkage. The presence of one or more physical dependence symptoms in combination with Feighner criteria alcoholism provided some evidence favoring linkage (TaqI A and D4). Alcoholics with an earlier onset of alcoholism showed some evidence for linkage especially when the presence of physical dependence was required (e.g., morning drinking, wanted to stop drinking but could not, binges or benders, and evidence of withdrawal symptoms). Finally, alcoholics with antisocial personality disorder differed significantly in their allele sharing from non-alcoholics for both D2 polymorphisms. Am.
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