Identification of Genetic Variants for Diabetic Retinopathy Risk Applying Exome Sequencing in Extreme Phenotypes

Area of Science:

• Genetics
• Ophthalmology
• Population Health

Background:

• Diabetic retinopathy (DR) risk varies by ethnicity, necessitating analysis of underrepresented populations for genetic variants.
• Mexican population was studied to identify genetic variants associated with DR risk.

Purpose of the Study:

• To identify genetic variants associated with diabetic retinopathy (DR) risk in the Mexican population.
• To analyze differences in rare variant frequencies between DR cases and controls.

Main Methods:

• A case-control study involving 60 type 2 diabetes mellitus (T2DM) patients (30 with proliferative DR, 30 without DR).
• Exome sequencing was performed, and frequencies of rare variants and variants in 169 DR-associated genes were compared.

Main Results:

• Statistically significant differences were found for rare missense and splice variants, particularly those occurring more than once.
• A significant difference was observed in rare missense variants with predicted pathogenicity (p = 0.0035).
• Eight variants in previously identified DR-associated genes were found more than once; the KIR2DS4 p.Pro234Ser variant showed a protective effect (OR = 0.04).

Conclusions:

• Enrichment of rare splice acceptor/donor variants observed in proliferative DR patients.
• A potential protective variant, KIR2DS4 p.Pro234Ser, was identified.
• Results support the replication of 8 previously identified DR-associated genes in this population.