Association of CTXN3-SLC12A2 Polymorphisms and Schizophrenia in a Thai Population

Overview

Journal Behav Brain Funct

Publisher Biomed Central

Specialties Neurology
Psychology
Social Sciences

Date 2012 May 31

PMID 22643131

Citations 5

Authors

Benjaporn Panichareon

Kazuhiro Nakayama

Sadahiko Iwamoto

Wanpen Thurakitwannakarn

Wasana Sukhumsirichart

Affiliations

Soon will be listed here.

Abstract

Background: A genome-wide association study (GWAS) combined with brain imaging as a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region were related to forebrain development and stress response which involved in schizophrenia. In the present study, the SNPs in this region were analyzed for association with schizophrenia in a Thai population.

Methods: A total of 115 schizophrenia and 173 unrelated normal controls with mean age of 37.87 ± 11.8 and 42.81 ± 6.0 years, respectively, were included in this study. Genotyping was performed using polymerase chain reaction and high-resolution melting (HRM) analysis. The difference in genotype distribution between patient and control was assessed by Chi-square test of the SPSS software.

Results: We found a significant association between the GWAS-discovered SNP, rs245178, with the risk of schizophrenia in the Thai population [P = 0.006, odds ratio for the minor G allele: 0.62(0.46-0.83)]. Additionally, another potential SNP, rs698172, which was in moderate linkage disequilibrium with rs245178, also showed strong association with schizophrenia [P = 0.003, odds ratio for minor T allele: 0.61(0.46-0.82)]. This association remained significant at 5% level after the Bonferroni correction for multiple testing.

Conclusions: This study shows that two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are associated with risk of schizophrenia in Thai population. Further study is required for clarification the role of genetic variation around these SNPs in expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in schizophrenia pathogenesis.

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References

Andreasen N, Flaum M . Schizophrenia: the characteristic symptoms. Schizophr Bull. 1991; 17(1):27-49. DOI: 10.1093/schbul/17.1.27. View

Almasy L, Gur R, Haack K, Cole S, Calkins M, Peralta J . A genome screen for quantitative trait loci influencing schizophrenia and neurocognitive phenotypes. Am J Psychiatry. 2008; 165(9):1185-92. PMC: 2644284. DOI: 10.1176/appi.ajp.2008.07121869. View

Panichareon B, Nakayama K, Thurakitwannakarn W, Iwamoto S, Sukhumsirichart W . OPCML gene as a schizophrenia susceptibility locus in Thai population. J Mol Neurosci. 2011; 46(2):373-7. DOI: 10.1007/s12031-011-9595-2. View

Tandon R, Nasrallah H, Keshavan M . Schizophrenia, "just the facts" 4. Clinical features and conceptualization. Schizophr Res. 2009; 110(1-3):1-23. DOI: 10.1016/j.schres.2009.03.005. View

Wang H, Chang J, Guo Z, Li B . In silico-initiated cloning and molecular characterization of cortexin 3, a novel human gene specifically expressed in the kidney and brain, and well conserved in vertebrates. Int J Mol Med. 2007; 20(4):501-10. View

Barrett J, Fry B, Maller J, Daly M . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2004; 21(2):263-5. DOI: 10.1093/bioinformatics/bth457. View

Faul F, Erdfelder E, Lang A, Buchner A . G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007; 39(2):175-91. DOI: 10.3758/bf03193146. View

Kendler K, Diehl S . The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull. 1993; 19(2):261-85. DOI: 10.1093/schbul/19.2.261. View

Payne J, Xu J, Haas M, Lytle C, Ward D, Forbush 3rd B . Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon. J Biol Chem. 1995; 270(30):17977-85. DOI: 10.1074/jbc.270.30.17977. View

10.

ODonovan M, Craddock N, Norton N, Williams H, Peirce T, Moskvina V . Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008; 40(9):1053-5. DOI: 10.1038/ng.201. View

11.

Cardno A, Marshall E, Coid B, MacDonald A, Ribchester T, Davies N . Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry. 1999; 56(2):162-8. DOI: 10.1001/archpsyc.56.2.162. View

12.

Stephens M, Donnelly P . A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet. 2003; 73(5):1162-9. PMC: 1180495. DOI: 10.1086/379378. View

13.

Potkin S, Turner J, Guffanti G, Lakatos A, Fallon J, Nguyen D . A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophr Bull. 2008; 35(1):96-108. PMC: 2643953. DOI: 10.1093/schbul/sbn155. View

14.

Lewis C, Levinson D, Wise L, DeLisi L, Straub R, Hovatta I . Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet. 2003; 73(1):34-48. PMC: 1180588. DOI: 10.1086/376549. View

15.

Dzhala V, Talos D, Sdrulla D, Brumback A, Mathews G, Benke T . NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005; 11(11):1205-13. DOI: 10.1038/nm1301. View

16.

Zintzaras E, Santos M . Estimating the mode of inheritance in genetic association studies of qualitative traits based on the degree of dominance index. BMC Med Res Methodol. 2011; 11:171. PMC: 3299619. DOI: 10.1186/1471-2288-11-171. View

17.

Coulter 2nd P, Bautista E, Margulies J, Watson J . Identification of cortexin: a novel, neuron-specific, 82-residue membrane protein enriched in rodent cerebral cortex. J Neurochem. 1993; 61(2):756-9. DOI: 10.1111/j.1471-4159.1993.tb02183.x. View

18.

Dworkin R, Lenzenweger M . Symptoms and the genetics of schizophrenia: implications for diagnosis. Am J Psychiatry. 1984; 141(12):1541-6. DOI: 10.1176/ajp.141.12.1541. View

19.

Zintzaras E . The generalized odds ratio as a measure of genetic risk effect in the analysis and meta-analysis of association studies. Stat Appl Genet Mol Biol. 2010; 9:Article21. DOI: 10.2202/1544-6115.1542. View