title: The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy.
abstract: Genetic factors could be implicated in the pathogenesis of severe diabetic retinopathy (DR). Recently, we reported a strong association between the eNOS4b/a endothelial nitric oxide synthase (eNOS) polymorphism and severe DR. To examine whether T-786C and C774T eNOS polymorphisms are involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped. The distribution of T-786C and C774T eNOS polymorphisms was in Hardy-Weinberg equilibrium and did not differ between the study and control groups. However, in case patients (n=126), T-786C and C774T polymorphisms influenced the onset pattern of severe DR (P=0.0169 and P=0.0257, respectively). The C-786C genotype was associated with early-onset severe DR (duration of diabetes: 15.2+/-5.9 vs. 19.4+/-6.3 years, P=0.0105), and the homozygous T774T genotype was associated with late-onset severe DR (24.3+/-7.0 vs. 18.4+/-6.2 years, P=0.0067). In the case of patients with high glycosylated hemoglobin levels (HbA1c >8%, n=88), the association between the T-786C polymorphism and early-onset severe DR was stronger (P=0.0068). Case patients carrying the C-786C genotype had higher HbA1c values (9.61+/-1.89%) than those carrying the T-786T genotype (8.93+/-1.47%, P=0.0173). Multivariate analysis showed that T-786C polymorphism was the best independent factor for onset pattern of severe DR (P<0.001). These findings, supported by previous associations between eNOS4b/a polymorphism and DR, suggest that T-786C and C774T eNOS polymorphisms affect the onset pattern of severe DR.
authors.affiliation: INSERM U.341, Department of Diabetology, Hôtel-Dieu Hospital, Paris, France. taverna1@yahoo.fr
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Taverna
authors.forename: Fabienne
authors.initials: F
authors.lastname: Elgrably
authors.forename: Henri
authors.initials: H
authors.lastname: Selmi
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Selam
authors.forename: Gérard
authors.initials: G
authors.lastname: Slama
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III