The e4 allele of apolipoprotein E gene is a potential risk factor for the severity of macular edema in type 2 diabetic Mexican patients

Santos, Arturo; Salguero, Mario L.; Gurrola, Carmen; Muñoz, Francisco J.; Roig-Melo, Enrique A; Panduro, Arturo

doi:10.1076/opge.23.1.13.2203

Cited by 29 publications

(15 citation statements)

References 7 publications

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“…The allelic variation at the APOE locus contributes to lipid profile variation and has been suggested to be a risk factor for the development of micro-and macrovascular complications in diabetic patients in several studies, but not in all populations (16). There are, however, very few studies of this polymorphic system in DR, particularly for DM2 (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Errera¹,

Silva

Yeh

et al. 2006

Braz J Med Biol Res

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Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and ε2/ε3/ε4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (ε2, ε3 and ε4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of ε2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/ 107 (6.5%); P < 0.05]. Therefore, our results suggest that the ε2 allele/ APOE might be a risk factor for diabetes in the Brazilian population.

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Section: Introductionmentioning

confidence: 99%

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Errera¹,

Silva

Yeh

et al. 2006

Braz J Med Biol Res

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“…By both association study and multiple logistic regression analysis, we found that the T-786C and 27-bp repeat polymorphisms were significantly associated with a risk of ME development, with the Ϫ786C and "a" alleles increasing the risk. Few reports have analyzed the susceptibility genes for ME; Santos et al (27) reported an association of apolipoprotein E gene with ME in a small population (36 patients with type 2 diabetes), and Kumaramanickavel et al (28) reported an association of aldose reductase gene with PDR and ME in 214 patients with type 2 diabetes.…”

Section: Enos Gene and Diabetic Macular Edemamentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

et al. 2004

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OBJECTIVE -We examined the endothelial nitric oxide (eNOS) gene polymorphisms to assess its possible association with diabetic retinopathy and macular edema.RESEARCH DESIGN AND METHODS -A total of 226 patients with type 2 diabetes and 186 healthy subjects were studied. Type 2 diabetic patients consisted of 110 patients without retinopathy, 46 patients with nonproliferative diabetic retinopathy, and 71 patients with proliferative diabetic retinopathy. Diabetic macular edema was present in 48 patients. Three polymorphisms of the eNOS gene were determined: T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7.RESULTS -Close linkage disequilibrium was observed between the T-786C polymorphism and the 27-bp repeat, as has been previously reported, but Glu298Asp was not in linkage disequilibrium with the other two polymorphisms. The eNOS gene polymorphisms were not significantly associated with the presence of retinopathy or with retinopathy severity or type 2 diabetes itself. However, by both association study and multiple logistic regression analysis, the T-786C and 27-bp repeat polymorphisms were significantly associated with a risk of developing macular edema with the Ϫ786C allele and the "a" allele increasing the risk.CONCLUSIONS -The present study suggests that the eNOS gene is a novel genetic risk factor for diabetic macular edema. The eNOS gene polymorphisms may contribute to the development of macular edema by impairing basal eNOS expression and resulting in the breakdown of the blood-retina barrier. Diabetes Care 27:2184 -2190, 2004D iabetic retinopathy (DR) remains the major cause of blindness among adults (1). In addition, diabetic maculopathy or macular edema (ME), which may occur at any stage of DR, is an important cause of visual impairment (1-3). Among the pathophysiological steps involved in the development of ME, the most important mechanism is breakdown of the blood-retina barrier (BRB) (2,3). Both the inner BRB formed by the retinal capillary endothelial cell tight junctions and the outer BRB formed by the retinal pigment epithelial cell tight junctions can be affected during the development of ME.Nitric oxide (NO) is a multifunctional molecule that plays a key role in physiological processes such as the regulation of vascular tone and the antiproliferative effects on vascular smooth muscle cells (4,5). NO is produced by three different isoforms of NO synthase (NOS): endothelial NOS (eNOS), neural NOS, and inducible NOS (iNOS). Although NO produced in large amounts by iNOS is regarded as a toxic, damaging agent, it is suggested that a low concentration of NO produced by constitutively expressed eNOS is necessary to maintain good endothelial function (5). Thus, eNOS appears to present an attractive candidate susceptibility gene for diabetic microvascular complications as well as cardiovascular diseases.Several polymorphisms have been identified in the eNOS gene (NOS3) (6,7). In particular, T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7 have...

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“…In Mexico, Santos et al enrolled 36 patients with DR and 22 unrelated and apparently healthy age-matched individuals to determine the relationship between ApoE polymorphism and the severity of retinal hard exudate in Mexican patients with NIDDM [51]. The frequency of severe retinal hard exudate was higher in the epsilon4 allele carriers.…”

Section: Associations With Nontraditional Lipid Markersmentioning

confidence: 99%

Dyslipidemia and Diabetic Retinopathy

Chang

2013

Rev Diabet Stud

100

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■ AbstractDiabetic retinopathy (DR) is one of the major microvascular complications of diabetes. In developed countries, it is the most common cause of preventable blindness in diabetic adults. Dyslipidemia, a major systemic disorder, is one of the most important risk factors for cardiovascular disease. Patients with diabetes have an increased risk of suffering from dyslipidemia concurrently. The aim of this article is to review the association between diabetic retinopathy (DR) and traditional/nontraditional lipid markers, possible mechanisms involving lipid metabolism and diabetic retinopathy, and the effect of lipid-lowering therapies on diabetic retinopathy. For traditional lipid markers, evidence is available that total cholesterol and low-density lipoprotein cholesterol are associated with the presence of hard exudates in patients with DR. The study of nontraditional lipid markers is advancing only in recently years. The severity of DR is inversely associated with apolipoprotein A1 (ApoA1), whereas ApoB and the ApoB-to-ApoA1 ratio are positively associated with DR. The role of lipid-lowering medication is to work as adjunctive therapy for better control of diabetes-related complications including DR.

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The e4 allele of apolipoprotein E gene is a potential risk factor for the severity of macular edema in type 2 diabetic Mexican patients

Abstract: Our results suggest that the epsilon4 allele of the ApoE gene is a potential risk factor for the severity of retinal hard exudates and visual loss in type 2 diabetic Mexican patients with diabetic retinopathy.

Cited by 29 publications

References 7 publications

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients

Endothelial Nitric Oxide Synthase Gene Is Associated With Diabetic Macular Edema in Type 2 Diabetes

Dyslipidemia and Diabetic Retinopathy

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