Genetic study of diabetic retinopathy: recruitment methodology and analysis of baseline characteristics

Clin Exp Ophthalmol. 2014 Jul;42(5):486-93. doi: 10.1111/ceo.12239. Epub 2013 Oct 28.

Abstract

Background: Diabetic retinopathy (DR) is a blinding disease of increasing prevalence that is caused by a complex interplay of genetic and environmental factors. Here we describe the patient recruitment methodology, case and control definitions, and clinical characteristics of a study sample to be used for genome-wide association analysis to detect genetic risk variants of DR.

Methods: One thousand six hundred sixty-nine participants with either type 1 (T1) or type 2 (T2) diabetes mellitus (DM) aged 18 to 95 years were recruited in Australian hospital clinics. Individuals with T2DM had disease duration of at least 5 years and were taking oral hypoglycaemic medication, and/or insulin therapy. Participants underwent ophthalmic examination. Medical history and biochemistry results were collected. Venous blood was obtained for genetic analysis.

Results: Six hundred eighty-three diabetic cases (178 T1DM and 505 T2DM participants) with sight-threatening DR, defined as severe non-proliferative DR, proliferative DR or diabetic macular oedema were included in this analysis. Eight hundred twelve individuals with DM but no DR or minimal non-proliferative DR were recruited as controls (191 with T1DM and 621 with T2DM). The presence of sight-threatening DR was significantly correlated with DM duration, hypertension, nephropathy, neuropathy, HbA1C and body mass index. Diabetic macular oedema was associated with T2DM (P < 0.001), whereas proliferative DR was associated with T1DM (P < 0.001).

Conclusions: Adoption of a case-control study design involving extremes of the DR phenotype makes this a suitable cohort, for a well-powered genome-wide association study to detect genetic risk variants for DR.

Keywords: diabetic macular oedema; diabetic retinopathy; genome-wide association study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Retinopathy / genetics*
  • Female
  • Fluorescein Angiography
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Macular Edema / genetics*
  • Male
  • Middle Aged
  • Patient Selection*
  • Young Adult

Substances

  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human