Association Of Vascular Endothelial Growth Factor And Htra1 Gene Copy Number Variation With Age Related Macular Degeneration In The Korean Population

Abstract

Purpose: : Studies have shown that genetic factors are strongly associated with age related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in AMD patients and control subjects.

Methods: : Genomic DNA was extracted from 233 AMD patients and 251 control subjects. Among the AMD-relevant genes, candidates CNVs were selected based on common CNVs elucidated in Asian. Real-time PCR (RT-PCR) based TagMan Copy Number Assays were performed for VEGF-A, HTRA1, CFH and VLDLR genes. RNase P was chosen as a reference gene. Applied Biosystems CopyCaller^TM Software v1.0 was used to determine the copy number of each target region and each reaction was duplicated. CNV frequencies were compared between patients and controls using the Chi-square test.

Results: : Gain for VEGF-A was found more frequently in the AMD patients compared with the control (P=0.031). Loss for VEGF-A was found in 5 subjects of control group, whereas none of the AMD group presents VEGF-A loss. By contrast, gain for HTRA1 were found more frequently in controls than in AMD patients (P=0.0016). CNV frequency in CFH and VLDLR genes was not different between patients and control subjects.

Conclusions: : The CNVs located in VEGF-A and HTRA1 genes may be associated with AMD susceptibility.

Keywords: age-related macular degeneration • genetics • vascular endothelial growth factor