EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes.
OBJECTIVE
We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR).


METHODS
A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1-80C>A, IVS1-206G>C, IVS1-252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited.


RESULTS
A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms.


CONCLUSIONS
The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes.
Li
Haitao
H
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
Louey
Janice W C
JW
Choy
Kwong Wai
KW
Liu
David T L
DT
Chan
Wai Man
WM
Chan
Yiu Man
YM
Fung
Nicholas S K
NS
Fan
Bao Jian
BJ
Baum
Larry
L
Chan
Juliana C N
JC
Lam
Dennis S C
DS
Pang
Chi Pui
CP
D017668:Age of Onset; D000368:Aged; D001216:Asparagine / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000150:complications* / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis
D019332:Endothelin-1; D001216:Asparagine; D008239:Lysine