Abstract: Objective We intended to apply targeted capture and exome sequencing to identify genetic variants involved in proliferative diabetic retinopathy. Methods In this case-control study, all subjects were assessed using ophthalmoscopy and fundus photographs. Fifty subjects with proliferative diabetic retinopathy(with less than 15 years of diabetes duration) and 50 subjects without diabetic retinopathy(with hemoglobin A1c above 7.0%, at least 10 years of type 2 diabetes duration) were enrolled. The total DNA was extracted from the blood samples. Targeted capture and exome sequencing were applied. Results Subjects with proliferative diabetic retinopathy were younger and had shorter duration of diabetes. There were no significant differences in body mass index, blood pressure, hemoglobin A1c, lipid profiles and renal function between the proliferative diabetic retinopathy group and the non-diabetic retinopathy group. The prevalence of diabetic nephropathy in the proliferative diabetic retinopathy group(70.6%) was higher than that of the control group(21.6%, P=0.000). The average depth was 42-fold in exome sequencing. An excess of single nucleotide polymorphisms, particularly for nonsynonymous single nucleotide polymorphisms including 14 386 known and 6 444 novel single nucleotide polymorphisms, were identified. Conclusion These single nucleotide polymorphisms may be related with proliferative diabetic retinopathy in type 2 diabetes by applying targeted capture and exome sequencing. Further large-scale and experimental studies are needed to verify these associations.

Key words: proliferative diabetic retinopathy, genetic polymorphism, exome sequence, type 2