Association of SDF-1 and its receptor CXCR4 polymorphisms on the susceptibility of diabetic retinopathy in the Taiwanese population

Shu-Yen Peng; Chih-Chun Chuang; Yih-Shiou Hwang; Chieh-Hung Yen; Chia-Yi Lee; Shun-Fa Yang

doi:10.3389/fgene.2023.1296773

Association of SDF-1 and its receptor CXCR4 polymorphisms on the susceptibility of diabetic retinopathy in the Taiwanese population

Front Genet. 2023 Nov 23:14:1296773. doi: 10.3389/fgene.2023.1296773. eCollection 2023.

Authors

Shu-Yen Peng^{1

2}, Chih-Chun Chuang^{1

3

4}, Yih-Shiou Hwang^{2

5

6

7}, Chieh-Hung Yen^{2

6

8

9}, Chia-Yi Lee^{1

2

10}, Shun-Fa Yang^{1

11}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
² Department of Ophthalmology, Jen-Ai Hospital, Taichung, Taiwan.
³ Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan.
⁴ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁵ Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁶ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Ophthalmology, Chang Gung Memorial Hospital, Xiamen Branch, Xiamen, China.
⁸ Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
⁹ Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
¹⁰ Nobel Eye Institute, Taipei, Taiwan.
¹¹ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.

Abstract

Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine 4 (CXCR4) have been demonstrated to play critical roles in diabetic retinopathy (DR). This study investigated whether single-nucleotide polymorphisms (SNPs) of SDF-1 and its receptor CXCR4 are correlated with diabetic retinopathy (DR). Three SDF-1 SNPs, namely, rs1801157 (G/A), rs2297630 (G/A), and rs266085 (T/C), and two CXCR4 SNPs, namely, rs2228014 (C/T) and rs6430612 (C/T), were chosen and genotyped via the TaqMan allelic discrimination for 454 non-DR subjects and 276 DR individuals. Our results revealed that subjects carrying SDF-1 SNP rs2297630 GA (AOR: 2.962, 95% CI: 1.279-6.861, p = 0.011) and SDF-1 SNP rs2297630 GA + AA (AOR: 3.095, 95% CI: 1.394-6.872, p = 0.006) had significantly higher risk in the non-proliferative diabetic retinopathy (NPDR) groups than in the non-DR group. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal revealed that SDF-1 SNP rs2297630 GA and AA genotypic variants have higher SDF-1 expression than the GG wild-type alleles (p = 0.000016). In conclusion, our findings revealed that SDF-1 SNP rs2297630 was associated with NPDR.

Keywords: CXCR4; SDF-1; diabetic retinopathy; proliferative diabetic retinopathy; single-nucleotide polymorphisms.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Jen-Ai Hospital, Taichung, Taiwan, Grant Number JMRPGJM0051.