title: Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy.
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).
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Saba
authors.initials: S
authors.lastname: Saleem
authors.affiliation: Institute of Ophthalmology, Mayo Hospital, Lahore, Pakistan.
authors.forename: Aisha
authors.initials: A
authors.lastname: Azam
authors.affiliation: Royal College of Ophthalmologists, Mersey Deanery, United Kingdom.
authors.forename: Sundus Ijaz
authors.initials: SI
authors.lastname: Maqsood
authors.affiliation: Institute of Ophthalmology, Mayo Hospital, Lahore, Pakistan.
authors.forename: Irfan
authors.initials: I
authors.lastname: Muslim
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Shaheena
authors.initials: S
authors.lastname: Bashir
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Nosheen
authors.initials: N
authors.lastname: Fazal
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Moeen
authors.initials: M
authors.lastname: Riaz
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Syeda Hafiza Benish
authors.initials: SH
authors.lastname: Ali
authors.affiliation: Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan.|Army Medical College, Rawalpindi, Pakistan.
authors.forename: Muhammad Khizar
authors.initials: MK
authors.lastname: Niazi
authors.affiliation: Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan.|Army Medical College, Rawalpindi, Pakistan.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Ishaq
authors.affiliation: Tufts University Medical School, Boston, Massachusetts, United States of America.
authors.forename: Nadia Khalida
authors.initials: NK
authors.lastname: Waheed
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.|Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan.|Pakistan Academy of Sciences, Islamabad, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D007438:Introns; D008297:Male; D008875:Middle Aged; D010154:Pakistan; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A