Association between neuronal cell adhesion molecule (NRCAM) single nucleotide polymorphisms and schizophrenia in a Korean population

WE EVALUATED POLYMORPHISMS of the neuronal cell adhesion molecule (NRCAM) gene for an association study with schizophrenia because this gene plays a crucial role in synapse formation and maturation of the nervous system.1 Previous reports have shown the association between NRCAM and several psychiatric disorders.2-4 In this study, the association between polymorphisms of NRCAM and schizophrenia in the Korean population was investigated. A total of 285 schizophrenic patients (185 male, 42.8 ± 10.9 years [mean ± SD]; 100 female, 42.9 ± 10.8) and 302 control subjects (145 male, 39.9 ± 5.8; 157 female, 33.5 ± 6.2) were evaluated. All patients were diagnosed by two well-trained psychiatrists according to the Diagnostic Statistical Manual of Mental Disorders, 4th edition. Written informed consent was obtained from all subjects. The study was approved by the ethics review committee of the Medical Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea. We searched for all single nucleotide polymorphisms (SNP) of the NRCAM gene region in human SNP databases (http://www.ensembl.org; http://www.ncbi.nlm.nih.gov/SNP; http://www.hapmap.org) and finally selected 13 SNP. The selected 13 SNP consisted of three exonic SNP (rs1802993, rs1043895, and rs1269634), six intronic SNP within an average distance of 300 bp from the nearest exon (rs2142325, rs6970656, rs722519, rs6954366, rs1990162, and rs917251), three promoter SNP (rs3763463, rs10235968, and rs6967368), and one SNP near the 3′ gene region (rs17155059). Multiple logistic regression models were used to calculate the odds ratio, 95% confidence interval, and corresponding P-values, controlling for age and gender as covariables, and to analyze associations between SNP and schizophrenia. Of the 13 SNP examined, seven were polymorphic. The genotype distributions of five SNP (rs1990162, rs917251, rs3763463, rs10235968, and rs6967368) were in Hardy–Weinberg equilibrium (HWE; P > 0.05). Two SNP (rs1269634 and rs6970656) were not in HWE (P < 0.05). As a result, none of five SNP were associated with schizophrenia (P > 0.05; P-value was corrected using the Bonferroni method). Using the Gabriel method, two linkage disequilibrium blocks were revealed (block 1 comprised rs917251 and rs3763463; block 2 consisted of rs10235968 and rs6967368). However, we did not detect significant associations between the haplotypes in block 1 or 2 and schizophrenia. The result indicates that NRCAM do not contribute to a genetic susceptibility to schizophrenia. Received 28 March 2008; revised 7 August 2008; accepted 12 August 2008. This study was supported by grants from the SRC program of KOSEF (R11-2005-014), Republic of Korea.