Cortical NMDA Receptor Expression in Human Chronic Alcoholism: Influence of the TaqIA Allele of ANKK1

• Published in: Neurochemical research Vol. 34; no. 10; pp. 1775 - 1782
• Main Authors: Ridge, Justin P., Dodd, Peter R.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2009; Springer Nature B.V
• Subjects: Alcoholism - genetics; Alcoholism - metabolism; Alcoholism - pathology; Alleles; Ankyrin Repeat - genetics; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cerebral Cortex - pathology; Cerebral Cortex - physiology; Female; Gene Expression Regulation, Enzymologic; Genotype; Humans; Male; Middle Aged; Neurochemistry; Neurology; Neurosciences; Original Paper; Polymorphism, Genetic - physiology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - physiology; Receptors, N-Methyl-D-Aspartate - biosynthesis; Receptors, N-Methyl-D-Aspartate - genetics; Taq Polymerase - genetics; Taq Polymerase - physiology; Alcohol dependence; Genetic susceptibility; Pathogenesis; Excitotoxicity
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-009-9941-8

Real-time RT-PCR normalized to GAPDH was used to assay N -methyl- d -aspartate (NMDA) receptor NR1, NR2A and NR2B subunit mRNA in human autopsy cortex tissue from chronic alcoholics with and without comorbid cirrhosis of the liver and matched controls. Subunit expression was influenced by the subject’s genotype. The Taq IA polymorphism selectively modulated NMDA receptor mean transcript expression in cirrhotic-alcoholic superior frontal cortex, in diametrically opposite ways in male and female subjects. Genetic make-up may differentially influence vulnerability to brain damage by altering the excitation: inhibition balance, particularly in alcoholics with comorbid cirrhosis of the liver. The Taq IA polymorphism occurs within the poorly characterised ankyrin-repeat containing kinase 1 ( ANKK1 ) gene. Using PCR, ANKK1 mRNA transcript was detected in inferior temporal, occipital, superior frontal and primary motor cortex of control human brain. ANKK1 expression may mediate the influence of the Taq IA polymorphism on phenotype.