Abstract
Alcohol dependence (AD) is characterized by compulsive alcohol consumption, which involves behavioral impairments such as aggression. Members of fibroblast growth factor (FGF) 19 superfamily, including FGF19, FGF21, and FGF23, are major endocrine mediators that play an important role in alcohol metabolism and alcohol related disorders. The objective of the present study is to explore the possible associations among the interaction of single nucleotide polymorphisms (SNPs) of the FGF 19 superfamily, AD occurrence, and aggression in patients with AD. A total of 956 subjects were enrolled in this study, including 482 AD patients and 474 healthy controls (HCs). Michigan alcoholism screening test (MAST) was used to measure the level of AD, a Chinese version of the Buss–Perry Aggression Questionnaire was used to evaluate the aggressive behavior of subjects, and MassARRAY@ system was used to genotype rs948992 of FGF19, rs11665841 and rs11665896 of FGF21, rs7955866 and rs11063118 of FGF23. The results showed that AD patients presented a significantly higher level of aggression compared to HCs, and MAST scores were significantly positively associated Buss–Perry aggression scores (r = 0.402, p < 0.001) in AD patients. The interaction of FGF19 rs948992 TC × FGF21 rs11665896 GG presented the high-risk genotype combination predicting the high level of AD. In addition, the interaction of FGF19 rs948992 TC × FGF21 rs11665896 TG × FGF23 rs11063118 TT presented the high-risk genotype combination predicting the high level of aggression in AD patients. Our results added evidence linking the combination of rs948992 TC × rs11665896 TG × rs11063118 TT to aggressive behavior in AD patients and pointed out the potential usefulness of the SNPs of FGF19 superfamily as a predictor for the aggression in AD patients.
Highlights
Alcohol dependence (AD) is a common psychiatric disorder and is characterized by loss of control over alcohol drinking, which is associated with impaired decision-making, seeking alcohol regardless of health status and behavioral impairments such as aggression and impulsivity, even suicide attempts (Tobore, 2019; Witkiewitz et al, 2019)
In order to explore the possible associations of fibroblast growth factor (FGF) 19, 21, and 23 polymorphisms with AD and AD-related aggression, rs948992 of FGF19, rs11665841, and rs11665896 of FGF21, and rs7955866 and rs11063118 of FGF23 were chosen to evaluate genotypes by using MassARRAY@ system, Michigan alcoholism screening test (MAST) was used to measure the level of AD, and a Chinese version of the Buss–Perry Aggression Questionnaire was used to evaluate the aggressive behavior of subjects in the present study
We found the interaction of FGF19 rs948992 TC × FGF21 rs11665896 GG presented the high-risk genotype combination associated with AD
Summary
Alcohol dependence (AD) is a common psychiatric disorder and is characterized by loss of control over alcohol drinking, which is associated with impaired decision-making, seeking alcohol regardless of health status and behavioral impairments such as aggression and impulsivity, even suicide attempts (Tobore, 2019; Witkiewitz et al, 2019). The environmental factors and specific genes may be the important causes for AD and alcoholuse disorders including aggression (Schuckit, 2009; Plemenitas et al, 2015). The interaction among the single nucleotide polymorphisms (SNPs) of genes of oxytocin and its receptor was reported to be related to alcohol disorder and aggressive behavior (Yang et al, 2017). The GABA type A receptor subunit alpha (GABRA) 2 rs279826/rs279858 A-allele interacts with stress, contributing to the development of alcohol use and aggressive behavior (Kiive et al, 2017)
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