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


METHODS
227 outpatients with schizophrenia (DSM-IV criteria) and 420 unrelated healthy controls from Asturias (Northern Spain) were genotyped using standard methods.


RESULTS
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 (chi(2) (3)=11.51, p=0.009), whereby the combination of -1438A and 5-HTTLPR S alleles was associated with schizophrenia.


CONCLUSIONS
Our findings support a possible synergistic effect of genetic factors influencing serotonergic neurotransmission on susceptibility to schizophrenia.
Sáiz
Pilar A
PA
Department of Psychiatry, School of Medicine, University of Oviedo, Julián Clavería 6 - 3 degrees, 33006 Oviedo, Spain. frank@uniovi.es
García-Portilla
M Paz
MP
Arango
Celso
C
Morales
Blanca
B
Alvarez
Victoria
V
Coto
Eliécer
E
Fernández
Juan M
JM
Bascarán
M Teresa
MT
Bousoño
Manuel
M
Bobes
Julio
J
D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013030:Spain
D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins