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Association of NKAPL, TSPAN18, and MPC2 gene variants with schizophrenia based on new data and a meta-analysis in Han Chinese

Published online by Cambridge University Press:  27 July 2016

Zhen Li ,
Tingting Shen ,
Ran Xin ,
Baoyun Liang ,
Juan Jiang ,
Weijun Ling ,
Bo Wei  and
Li Su
Zhen Li
Affiliation:
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China Education Department, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
Tingting Shen
Affiliation:
First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Ran Xin
Affiliation:
Chinese Center for Disease Control and Prevention, Nanning, Guangxi, China
Baoyun Liang
Affiliation:
First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi, China
Juan Jiang
Affiliation:
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
Weijun Ling
Affiliation:
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
Bo Wei*
Affiliation:
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
Li Su*
Affiliation:
School of Public Health, Guangxi Medical University, Nanning, Guangxi, China Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Nanning, Guangxi, China
*
Bo Wei, School of Public Health of Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi 530021, China. Tel: +867 715 358 847; Fax: +867 715 350 823; E-mail: [email protected]
Li Su, School of Public Health of Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi 530021, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Nanning, Guangxi 530021, China. Tel: +861 387 889 0526; Fax: +867 715 350 823; E-mail: [email protected]
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Abstract

Background

Schizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between the NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms and SZ in a Chinese population.

Methods

This study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han). The polymorphisms in TSPAN18 (rs11038167), NKAPL (rs1635), and MPC2 (rs10489202) were genotyped using the Sequenom MassARRAY method. Statistical analyses were performed with PLINK program and SPSS l6.0 for Windows. STATA11.1 was used for meta-analysis.

Results

No statistically significant difference was found in different allele and genotype frequencies of rs1635, rs11038167, and rs10489202 between SZ cases and controls of Zhuang and Han ethnicities and the total samples (all p>0.05). Further meta-analysis suggested that single-nucleotide polymorphism rs10489202 was significantly associated with SZ in a Han Chinese population (pOR=0.002).

Conclusions

Our case–control study failed to validate the significant association of NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms with SZ susceptibility in the southern Zhuang or Han Chinese population. However, meta-analysis showed a significant association between MPC2 variant rs10489202 and SZ susceptibility in Han Chinese.

Keywords

association studiesMPC2NKAPLschizophreniaTSPAN18
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 29 , Issue 2 , April 2017 , pp. 87 - 94
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Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

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Footnotes

†

First co-author.

References

1. Owen, MJ, Craddock, N, O’Donovan, MC. Schizophrenia: genes at last? Trends Genet 2005;21:518–525.CrossRefGoogle ScholarPubMed
2. Saha, S, Chant, D, Welham, J, McGrath, J. A systematic review of the prevalence of schizophrenia. PLoS Med 2005;2:e141.Google Scholar
3. Jia, P, Wang, L, Meltzer, HY, Zhao, Z. Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data. Schizophr Res 2010;122:38–42.Google Scholar
4. Sullivan, PF, Daly, MJ, O’Donovan, M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012;13:537–551.Google Scholar
5. Yue, WH, Wang, HF, Sun, LD et al. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet 2011;43:1228–1231.CrossRefGoogle Scholar
6. Shi, Y, Li, Z, Xu, Q et al. Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nat Genet 2011;43:1224–1227.CrossRefGoogle ScholarPubMed
7. Purcell, SM, Wray, NR, Stone, JL et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009;460:748–752.Google Scholar
8. Shi, J, Levinson, DF, Duan, J et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009;460:753–757.Google Scholar
9. Stefansson, H, Ophoff, RA, Steinberg, S et al. Common variants conferring risk of schizophrenia. Nature 2009;460:744–747.CrossRefGoogle ScholarPubMed
10. Jia, P, Wang, L, Fanous, AH, Chen, X, Kendler, KS, Zhao, Z. A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia. J Med Genet 2012;49:96–103.Google Scholar
11. Mexal, S, Frank, M, Berger, R et al. Differential modulation of gene expression in the NMDA postsynaptic density of schizophrenic and control smokers. Brain Res Mol Brain Res 2005;139:317–332.Google Scholar
12. Harrison, PJ. The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology (Berl) 2004;174:151–162.CrossRefGoogle ScholarPubMed
13. Berditchevski, F, Odintsova, E. Tetraspanins as regulators of protein trafficking. Traffic 2007;8:89–96.Google Scholar
14. Yuan, J, Jin, C, Qin, HD et al. Replication study confirms link between TSPAN18 mutation and schizophrenia in Han Chinese. PLoS One 2013;8:e58785.Google Scholar
15. Halestrap, AP, Scott, RD, Thomas, AP. Mitochondrial pyruvate transport and its hormonal regulation. Int J Biochem 1980;11:97–105.Google Scholar
16. Khaitovich, P, Lockstone, HE, Wayland, MT et al. Metabolic changes in schizophrenia and human brain evolution. Genome Biol 2008;9:R124.Google Scholar
17. Olsen, L, Hansen, T, Jakobsen, KD et al. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples. BMC Med Genet 2008;9:39.Google Scholar
18. Ma, L, Tang, J, Wang, D et al. Evaluating risk loci for schizophrenia distilled from genome-wide association studies in Han Chinese from Central China. Mol Psychiatry 2013;18:638–639.Google Scholar
19. Jin, C, Zhang, Y, Wang, J et al. Lack of association between MPC2 variants and schizophrenia in a replication study of Han Chinese. Neurosci Lett 2013;552:120–123.Google Scholar
20. Chen, SF, Chao, YL, Shen, YC, Chen, CH, Weng, CF. Resequencing and association study of the NFKB activating protein-like gene (NKAPL) in schizophrenia. Schizophr Res 2014;157:169–174.Google Scholar
21. Zhang, B, Li, DX, Lu, N, Fan, QR, Li, WH, Feng, ZF. Lack of association between the TSPAN18 gene and schizophrenia based on new data from Han Chinese and a meta-analysis. Int J Mol Sci 2015;16:11864–11872.Google Scholar
22. Wang, Z, Yang, B, Liu, Y et al. Further evidence supporting the association of NKAPL with schizophrenia. Neurosci Lett 2015;605:49–52.Google Scholar
23. Chen, J, Zheng, H, Bei, JX et al. Genetic structure of the Han Chinese population revealed by genome-wide SNP variation. Am J Hum Genet 2009;85:775–785.Google Scholar
24. Xu, S, Yin, X, Li, S et al. Genomic dissection of population substructure of Han Chinese and its implication in association studies. Am J Hum Genet 2009;85:762–774.Google Scholar
25. Vigueira, PA, McCommis, KS, Schweitzer, GG et al. Mitochondrial pyruvate carrier 2 hypomorphism in mice leads to defects in glucose-stimulated insulin secretion. Cell Rep 2014;7:2042–2053.CrossRefGoogle ScholarPubMed
26. Gray, LR, Rauckhorst, AJ, Taylor, EB. A method for multiplexed measurement of mitochondrial pyruvate carrier activity. J Biol Chem 2016;291:7409–7417.Google Scholar
27. Shetty, PK, Galeffi, F, Turner, DA. Cellular links between neuronal activity and energy homeostasis. Front Pharmacol 2012;3:43.CrossRefGoogle ScholarPubMed
28. Parnetti, L, Gaiti, A, Polidori, MC et al. Increased cerebrospinal fluid pyruvate levels in Alzheimer’s disease. Neurosci Lett 1995;199:231–233.CrossRefGoogle ScholarPubMed
28. Ahmed, SS, Santosh, W, Kumar, S, Christlet, HT. Metabolic profiling of Parkinson’s disease: evidence of biomarker from gene expression analysis and rapid neural network detection. J Biomed Sci 2009;16:63.Google Scholar
30. McCommis, KS, Finck, BN. Mitochondrial pyruvate transport: a historical perspective and future research directions. Biochem J 2015;466:443–454.Google Scholar
31. Zhang, Y, Lu, T, Yan, H et al. Replication of association between schizophrenia and chromosome 6p21-6p22.1 polymorphisms in Chinese Han population. PLoS One 2013;8:e56732.Google Scholar
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