Association study of serotonin 2A receptor (5-HT2A) and serotonin transporter (5-HTT) gene polymorphisms with schizophrenia

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 31; no. 3; pp. 741 - 745
• Main Authors: Sáiz, Pilar A., García-Portilla, M. Paz, Arango, Celso, Morales, Blanca, Alvarez, Victoria, Coto, Eliécer, Fernández, Juan M., Bascarán, M. Teresa, Bousoño, Manuel, Bobes, Julio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 13.04.2007; Elsevier
• Subjects: 5-HT2A polymorphisms; 5-HTT polymorphisms; Adult; Adult and adolescent clinical studies; Alleles; Biological and medical sciences; Chi-Square Distribution; Female; Gene Frequency; Genetic association; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Polymorphism, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptor, Serotonin, 5-HT2A - genetics; Schizophrenia; Schizophrenia - genetics; Serotonin Plasma Membrane Transport Proteins - genetics; Spain; Spain; df; OR; SNP; CI; LD; Schizophrenia; 5-HT2A polymorphisms; 5-HTT polymorphisms; 5-HT; Genetic association; VNTR; LRT; Psychosis; 5-HT2A serotonin receptor; Gene; Genetics; Carrier protein; Polymorphism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2007.01.012

To investigate (i) the association between four serotonergic polymorphisms (A-1438G and T102C of the 5-HT2A receptor gene, and 5-HTT VNTR and 5-HTTLPR of the 5-HT transporter gene) and schizophrenia and (ii) the potential interaction of those polymorphisms in the development of schizophrenia. 227 outpatients with schizophrenia (DSM-IV criteria) and 420 unrelated healthy controls from Asturias (Northern Spain) were genotyped using standard methods. Both groups showed Hardy–Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms are in complete linkage disequilibrium in our population. There was an apparent difference in the distribution of genotypes for the A-1438G (or T102C) polymorphisms ( p = 0.018, not significant after a Bonferroni correction). The 5-HT2A − 1438A (or 102T) allele was significantly more frequent in patients than controls (0.53 and 0.45, respectively; corrected p = 0.028, OR = 1.39 (95% CI = 1.11–1.75)). Genotype and allele distributions for 5-HTT polymorphisms were similar in both groups. However, assessment of the combined influence of 5-HT2A A-1438G and 5-HTTLPR polymorphisms demonstrated a significant effect ( χ 2 (3) = 11.51, p = 0.009), whereby the combination of − 1438A and 5-HTTLPR S alleles was associated with schizophrenia. Our findings support a possible synergistic effect of genetic factors influencing serotonergic neurotransmission on susceptibility to schizophrenia.