Associations of single nucleotide polymorphisms of VEGFR1 and smoking with age-related macular degeneration in Hui and Han populations from Ningxia region in China

Authors: Xiang Wei,  Chi Hao,  Xue Zhongqi,  Zhang Wen,  Sheng Xunlun,  Zhuang Wenjuan
DOI: 10.3760/cma.j.issn.2095-0160.2016.06.012
Published 2016-06-10
Cite as Chin J Exp Ophthalmol, 2016,34(6): 534-540.

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Background

Age-related macular degeneration (AMD) is a heritable, progressive degenerative disorder that triggers central visual impairment.Research demonstrated that the single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor 1 (VEGFR1) gene is associated with AMD in different population.However, the results varied among diversified ethnic origin composition and distinct regions.

Objective

This study was to investigate the associations between the SNPs of VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ningxia population in China.

Methods

A case-control study was conducted.Four hundreds and thirty-two AMD patients including 325 Han ethnic patients and 107 Hui ethnic patients were recruited from March 2011 to June 2015, and 906 ethnicity-and gender-matched age-related cataract patients were contemporaneously recruited as control group, including 698 Han ethnic patients and 208 Hui ethnic patients.Periphery blood sample of 5 ml was collected from the subjects and genomic DNA was prepared.Eight tagging SNPs loci were acquired to cover rs2281827, rs3936415, rs7337610, rs7981680, rs9554320, rs9554322, rs9582036 and rs9943922, and the genotypes of SNPs were detected by using MassARRAY™ time-of-flight mass spectrometry system.Chi-square test and multi-factor Logistic regression analysis were utilized to estimate the discrepancy of allele frequency and genotype distribution in Hui and Han AMD patients.Moreover, the correlation of AMD with smoking and age statue were further analyzed.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Ningxia Eye Hospital.Written informed consent was obtained before any relevant medical examination.

Results

There were significant differences in the age between AMD group and control group in both Han and Hui ethnicity (Han: P=0.000; Hui: P=0.009). The smoking exposure was significantly different between AMD group and control group in Han ethnicity (P=0.000), and smoking was the independent risk factor of AMD disease in Han ethnicity of Ningxia region (odds ratio[OR]=2.622, 95% confidence interval [CI]: 1.899-3.619). The allele frequencies of SNPs were not significantly different in the AMD patients between Han and Hui ethnicity (all at P>0.05). However, the allele frequencies and genotype distribution of rs7337610 and rs9554322 SNPs were significantly different between the AMD group and control group in both Han and Hui ethnicity (all at P=0.00). The genotype distribution of rs9582036 and rs9943922 SNPs was significantly different between the AMD group and control group in Han ethnicity (P=0.02, 0.00). Allelic G of rs7337610 was the protective factor of AMD disease in Han and Hui ethnicity (OR=0.354, 95%CI: 0.288-0.435; OR=0.446, 95%CI: 0.315-0.632), while allelic C of rs9554322 was the risk factor of AMD disease in Han and Hui ethnicity (OR=1.671, 95%CI: 1.234-2.262; OR=3.661, 95%CI: 2.156-6.218). Allelic A of rs9582036 was the risk factor of AMD disease in Han ethnicity (OR=1.477, 95%CI: 1.124-1.940).

Conclusions

Smoking is the independent risk component for Han population with AMD.Of the eight SNPs tagged, the genotypes and alleles of rs9554322 and rs7337610 seems to confer susceptibility to AMD in both Han and Hui ethnicity, the genotypes and alleles of rs9582036 and rs9943922 confer susceptibility to AMD in only Han ethnicity.

Key words:

Vascular endothelial growth factor receptor-1/genetics; Macular degeneration/ethnology; Polymorphism, single nucleotide/genetics; Risk factors; Odds ratio; Genetic predisposition to disease; Alleles; Smoking/adverse effect; Case-control studies

Contributor Information

Xiang Wei
School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China
Chi Hao
School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China
Xue Zhongqi
School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China
Zhang Wen
School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China
Sheng Xunlun
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750001, China
Zhuang Wenjuan
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750001, China
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