Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors

Chen, Chian-Feng; Liou, Shiow-Wen; Wu, Hsin-Han; Lin, Chin-Hui; Huang, Li-Shan; Woung, Lin-Chung; Tsai, Ching-Yao

doi:10.7150/ijms.16345

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Int J Med Sci 2016; 13(9):717-723. doi:10.7150/ijms.16345 This issue Cite

Research Paper

Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors

Chian-Feng Chen¹, Shiow-Wen Liou^2,3,4,5, Hsin-Han Wu¹, Chin-Hui Lin¹, Li-Shan Huang⁶, Lin-Chung Woung^2,5,7,8,9, Ching-Yao Tsai^{2, 9✉}

1. VYM Genome Research Center, National Yang-Ming University, Taipei, Taiwan;
2. Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan;
3. Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;
4. Department of Ophthalmology, Taipei Medical University, Taipei, Taiwan;
5. Department of Ophthalmology, Taiwan University Hospital, Taipei, Taiwan;
6. Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan;
7. Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan;
8. Department of Medicine, National Yang-Ming University, Taipei, Taiwan;
9. Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.

Citation:

Chen CF, Liou SW, Wu HH, Lin CH, Huang LS, Woung LC, Tsai CY. Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors. Int J Med Sci 2016; 13(9):717-723. doi:10.7150/ijms.16345. https://www.medsci.org/v13p0717.htm

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Abstract

Objectives: Diabetic retinopathy (DR) is a common microvascular complication in both type I and type II diabetes. Several previous reports indicated the serum centration of some secretary factors were highly associated with DR. Therefore, we hypothesis regulatory SNPs (rSNPs) genotype in secretary factors may alter these gene expression and lead to DR.

Methods: At first, pyrosequencing were applying to screen the SNPs which present allele frequency different in DR and DNR. Then individual genotyping was processed by Taqman assays in Taiwanese DR and DNR patients. To evaluate the effect of SNP allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs.

Results: We found the frequencies of the CC, CG, and GG genotype of the rs2010963 polymorphism were 15.09%, 47.14%, and 37.74% in DR and 12.90%, 19.35%, and 67.74% in DNR, respectively (p = 0.0205). The prevalence of DR was higher (p = 0.00793) in patients with the CC or CG genotype (62.26% and 32.26% for DR and DNR, respectively) compared with the patients with the GG genotype. To evaluate the effect of rs2010963-C allele on transcriptional activity, we measured promoter activity using luciferase reporter constructs. The rs2010963-C reporter showed 1.6 to 2-fold higher luciferase activity than rs2010963-G in 3 cell lines.

Conclusion: Our data proposed rs2010963-C altered the expression level of VEGFA in different tissues. We suggested small increase but long term exposure to VEGFA may lead to DR finally.

Keywords: DR, SNP, VEGFA.

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APA

Chen, C.F., Liou, S.W., Wu, H.H., Lin, C.H., Huang, L.S., Woung, L.C., Tsai, C.Y. (2016). Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors. International Journal of Medical Sciences, 13(9), 717-723. https://doi.org/10.7150/ijms.16345.

ACS

Chen, C.F.; Liou, S.W.; Wu, H.H.; Lin, C.H.; Huang, L.S.; Woung, L.C.; Tsai, C.Y. Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors. Int. J. Med. Sci. 2016, 13 (9), 717-723. DOI: 10.7150/ijms.16345.

NLM

CSE

Chen CF, Liou SW, Wu HH, Lin CH, Huang LS, Woung LC, Tsai CY. 2016. Regulatory SNPs Alter the Gene Expression of Diabetic Retinopathy Associated Secretary Factors. Int J Med Sci. 13(9):717-723.

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