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Abstract
In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR).
Highlights
Diabetic Retinopathy (DR) is one of the most damaging microvascular complication of diabetes mellitus and remains a major cause of visual morbidity among the developed and under developed countries [1, 2]
The multivariate-gender adjusted logistic regression analysis resulted in significant association of ID genotype with the development of DR and the sub-clinical class nonproliferative DR (NPDR), which remained significant even after the correction of the data by simultaneous inference (DR p = 0.03057 and NPDR p = 0.02054, Table 2)
In the current study of Pakistani type 2 diabetes mellitus (T2DM) subjects genetic association was studied of single nucleotide polymorphisms (SNPs) of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1), which belong to the Renin-Angiotensin System (RAS) and Plasminogen Activator System (PAS), respectively, we observed significant association of ACE polymorphism with DR and NPDR
Summary
Diabetic Retinopathy (DR) is one of the most damaging microvascular complication of diabetes mellitus and remains a major cause of visual morbidity among the developed and under developed countries [1, 2]. It severely damages the cellular and the structural components of the retinal vasculature resulting in vision impairment, while often leading to blindness [2]. DR is considered as the major cause of blindness in people of working age and is characterized by hyperglycemia, thickening of the basement membrane accompanying loss of pericytes, microaneurysms, dysfunction of the endothelial cell, microvascular infarcts and neovascularization, which can eventually lead to loss of vision due to hemorrhages and detachment of the retina [1]. Retinal thickening from leaky blood vessels, can develop at all stages of retinopathy. These conditions lead to irreversible vision loss [1]
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