The SNP43 (G/A) Polymorphism in CAPN10 Gene Confers an Increased Risk of Cognitive Impairment in Cerebral Small Vessel Disease

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2018 Jul 18

PMID 30014550

Citations 3

Authors

Kai Wu

Ying Cai

Affiliations

Soon will be listed here.

Abstract

Background: Cognitive impairment, significantly reducing processing speed and executive function, is the critical consequence of cerebral small vessel disease (SVD), in which genetic variations have been studied. In this study, we explore the role of SNP43 (G/A) and SNP63 (C/T) polymorphism in the CAPN10 on cognitive impairment process in cerebral SVD.

Methods: Cerebral SVD patients (n = 224) and healthy controls (n = 187) were recruited. The relationship between frequency distribution of SNP43 (G/A) and SNP63 (T/C) genotype and allele in CAPN10 gene, and cognitive impairment was examined. The independent risk factors for cognitive impairment in SVD were determined by logistic regression analysis.

Results: Accordingly, the frequency distribution of genotype and allele at SNP43 (G/A) was significantly different between cerebral SVD patients and healthy controls. Cerebral SVD patients with GG genotype were more susceptible for cognitive impairment, whereas cerebral SVD patients with GA + AA genotype were less possible to suffer from cognitive impairment, compared with those with GG genotype. And also, cerebral SVD does not include SNP63 (C/T) to associate with cognitive impairment, and SNP43 (G/A), total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were independent risk factors for cognitive impairment in SVD.

Conclusion: Our study provides evidence that SNP43 (G/A) in the CAPN10 gene increases the risk of cognitive impairment in SVD patients. Besides it is proven that, patients with G allele are more susceptible to suffer from cerebral SVD with worse cognitive impairment.

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The Association Between the rs2975760 and rs3792267 Single Nucleotide Polymorphisms of Calpain 10 (CAPN10) and Gestational Diabetes Mellitus.

Zhang X, Shi C, Wei L, Sun F, Ji L Med Sci Monit. 2019; 25:5137-5142.

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The SNP43 (G/A) polymorphism in CAPN10 gene confers an increased risk of cognitive impairment in cerebral small vessel disease.

Wu K, Cai Y J Clin Lab Anal. 2018; 32(9):e22615.

PMID: 30014550 PMC: 6816906. DOI: 10.1002/jcla.22615.

References

Miyazaki T, Miyazaki A . Dysregulation of Calpain Proteolytic Systems Underlies Degenerative Vascular Disorders. J Atheroscler Thromb. 2017; 25(1):1-15. PMC: 5770219. DOI: 10.5551/jat.RV17008. View

Wang W, Yang L, Tan L, Wu X, Jiang B, Shen X . Arg972 insulin receptor substrate-1 polymorphism and risk and severity of Alzheimer's disease. J Clin Neurosci. 2014; 21(7):1233-7. DOI: 10.1016/j.jocn.2013.09.028. View

Liebetrau M, Staufer B, Auerswald E, Gabrijelcic-Geiger D, Fritz H, Zimmermann C . Increased intracellular calpain detection in experimental focal cerebral ischemia. Neuroreport. 1999; 10(3):529-34. DOI: 10.1097/00001756-199902250-00016. View

He Q, Li Q, Zhao J, Wu T, Ji L, Huang G . Relationship between plasma lipids and mild cognitive impairment in the elderly Chinese: a case-control study. Lipids Health Dis. 2016; 15(1):146. PMC: 5011904. DOI: 10.1186/s12944-016-0320-6. View

Liu W, Apagyi K, McLeavy L, Ersfeld K . Expression and cellular localisation of calpain-like proteins in Trypanosoma brucei. Mol Biochem Parasitol. 2009; 169(1):20-6. DOI: 10.1016/j.molbiopara.2009.09.004. View

Brookes R, Hollocks M, Khan U, Morris R, Markus H . The Brief Memory and Executive Test (BMET) for detecting vascular cognitive impairment in small vessel disease: a validation study. BMC Med. 2015; 13:51. PMC: 4372040. DOI: 10.1186/s12916-015-0290-y. View

Orho-Melander M, Klannemark M, Svensson M, Ridderstrale M, Lindgren C, Groop L . Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. Diabetes. 2002; 51(8):2658-64. DOI: 10.2337/diabetes.51.8.2658. View

Oladnabi M, Musante L, Larti F, Hu H, Abedini S, Wienker T . New evidence for the role of calpain 10 in autosomal recessive intellectual disability: identification of two novel nonsense variants by exome sequencing in Iranian families. Arch Iran Med. 2015; 18(3):179-84. DOI: 0151803/AIM.008. View

Staszewski J, Piusinska-Macoch R, Brodacki B, Skrobowska E, Macek K, Stepien A . Risk of vascular events in different manifestations of cerebral small vessel disease: A 2-year follow-up study with a control group. Heliyon. 2017; 3(11):e00455. PMC: 5727612. DOI: 10.1016/j.heliyon.2017.e00455. View

10.

Pantoni L . Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010; 9(7):689-701. DOI: 10.1016/S1474-4422(10)70104-6. View

11.

Feng L, Nian S, Zhang J . The GG genotype of telomerase reverse transcriptase at genetic locus rs2736100 is associated with human atherosclerosis risk in the Han Chinese population. PLoS One. 2014; 9(1):e85719. PMC: 3897494. DOI: 10.1371/journal.pone.0085719. View

12.

Wu K, Cai Y . The SNP43 (G/A) polymorphism in CAPN10 gene confers an increased risk of cognitive impairment in cerebral small vessel disease. J Clin Lab Anal. 2018; 32(9):e22615. PMC: 6816906. DOI: 10.1002/jcla.22615. View

13.

Shang L, Huang J, Ding W, Chen S, Xue L, Ma R . Calpain: a molecule to induce AIF-mediated necroptosis in RGC-5 following elevated hydrostatic pressure. BMC Neurosci. 2014; 15:63. PMC: 4023497. DOI: 10.1186/1471-2202-15-63. View

14.

Zheng K, Wang H, Hou B, You H, Yuan J, Luo K . Malnutrition-inflammation is a risk factor for cerebral small vessel diseases and cognitive decline in peritoneal dialysis patients: a cross-sectional observational study. BMC Nephrol. 2017; 18(1):366. PMC: 5738894. DOI: 10.1186/s12882-017-0777-1. View

15.

Bodhini D, Radha V, Ghosh S, Sanapala K, Majumder P, Rao M . Association of calpain 10 gene polymorphisms with type 2 diabetes mellitus in Southern Indians. Metabolism. 2010; 60(5):681-8. DOI: 10.1016/j.metabol.2010.07.001. View

16.

Medeiros R, Kitazawa M, Chabrier M, Cheng D, Baglietto-Vargas D, Kling A . Calpain inhibitor A-705253 mitigates Alzheimer's disease-like pathology and cognitive decline in aged 3xTgAD mice. Am J Pathol. 2012; 181(2):616-25. DOI: 10.1016/j.ajpath.2012.04.020. View

17.

Hong Y, Eu K, Seow-Choen F, Fook-Chong S, Cheah P . GG genotype of cyclin D1 G870A polymorphism is associated with increased risk and advanced colorectal cancer in patients in Singapore. Eur J Cancer. 2005; 41(7):1037-44. DOI: 10.1016/j.ejca.2005.01.009. View

18.

Ostergaard L, Engedal T, Moreton F, Hansen M, Wardlaw J, Dalkara T . Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline. J Cereb Blood Flow Metab. 2015; 36(2):302-25. PMC: 4759673. DOI: 10.1177/0271678X15606723. View

19.

Zhang W, Zhao Z, Dai C, Zhang R, Chen J, Tian H . Correlation between Calpain-10 single-nucleotide polymorphisms and obstructive sleep apnea/hypopnoea syndrome with ischemic stroke in a Chinese population: A population-based study. Medicine (Baltimore). 2017; 96(16):e6570. PMC: 5406063. DOI: 10.1097/MD.0000000000006570. View

20.

Badrnya S, Assinger A, Volf I . Native high density lipoproteins (HDL) interfere with platelet activation induced by oxidized low density lipoproteins (OxLDL). Int J Mol Sci. 2013; 14(5):10107-21. PMC: 3676831. DOI: 10.3390/ijms140510107. View