The Interaction of Single Nucleotide Polymorphisms on Fibroblast Growth Factor 19 Superfamily Genes Is Associated With Alcohol Dependence-Related Aggression

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.

New developments in the biology of fibroblast growth factors

“…SNP analysis of Chinese patients with alcohol dependence identified a genetic interaction of specific SNPs in FGF19 and FGF21 that were predictive of high‐level alcohol dependence. The combination of these SNPs in FGF19 and FGF21 with a SNP in FGF23 was predictive of high‐level aggression and alcohol dependence (J. Xu, Wu, et al, 2021).…”

“…The combination of these SNPs in FGF19 and FGF21 with a SNP in FGF23 was predictive of high-level aggression and alcohol dependence (J. Xu, Wu, et al, 2021).…”

The role of FGF21 and its analogs on liver associated diseases

“…The other studies confirmed the role of FGF21 SNPs in addictive behaviors like eating habits and the amount of coffee consumption ( 48 – 51 ). Previous studies also showed the importance of FGF21 genetic variations in obesity (rs11665896) ( 50 ), fat and macronutrient intake (rs838147) ( 51 ), renal function in diabetic patients (rs2071699, rs838136, and rs499765) ( 52 ), and alcohol dependence (rs11665896) ( 53 ) which indirectly can have effects on steatosis of liver.…”

The Interaction Between Genetic Variant ZNF804A rs1344706 and Alcohol Withdrawal on Impulsivity: Evidence for the Diathesis-Stress Model

“…Demographic data including age and years of education were collected. Genotyping was performed as previously described ( 17 ). Briefly, genomic DNA was extracted from 5 ml peripheral blood of each participant with salting-out method, and the ZNF804A rs1344706 SNP was genotyped using MALDI-TOF based scalable MassARRAY System (Agena Bioscience, Inc., San Diego, CA, United States) with PCR primers: 5-TCAAAGCCTTATCTCTTCAC-3, 5-CCAGATAGATATCCAAGAAG-3, and single-base extension primer: 5-ACTGAAACAAAGAATCAAAAAC-3 for genotyping.…”