Association of PIP4K2A Polymorphisms with Alcohol Use Disorder

Abstract

Background: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. Methods: 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CШA). Results: Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. Conclusions: For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula.

Genetics and Genomics of Addiction

“…The human literature related to twin studies, copy number variations, and candidate gene studies, illustrates a role for various genetic factors in FASD susceptibility. Fedorenko et al [ 5 ] also explored alcohol use, assessing the association of phosphatidylinositol-5-phosphate-4-kinase type two α (PIP4K2A) polymorphisms with alcohol use disorder. Polymorphisms in PIP4K2a, a gene known to play a role in dopaminergic pathways, were tested for their association with AUD in a population of Russian men.…”

Life: Computational Genomics Applications in Life Sciences

“…The authors examined the effects of GRIN2A and GRIN2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2A/2B) polymorphisms on the clinical features of schizophrenia using SNPs genotyping. Note that this approach has been used for gene polymorphism studies in association with alcohol use disorder [22] and complex disorders such as metabolic syndrome [23] that are related to FTO (fat mass and obesity-associated) gene. Associations of the FTO gene polymorphic variants were in shown [23].…”