Association analysis of 374T/A (rs1800624) receptor for advanced glycation end-products (RAGE) gene polymorphism with diabetic retinopathy in Pakistani patients.

Shazia Qayyum,Abdul Khaliq Naveed,Muhammad Afzal

doi:10.12669/pjms.37.3.3670

Shazia Qayyum, Abdul Khaliq Naveed + Show 1 more

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https://doi.org/10.12669/pjms.37.3.3670

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Abstract

Objectives:to determine the relationship of 374T/A (rs1800624) polymorphism in the gene encoding RAGE with Type-2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) level in Pakistani patients.Methods:A case-control study, conducted from January 2017 to December 2018, involving 150 healthy controls (HC), 150 T2DM patients with no retinopathy (DNR) and 150 DR patients diagnosed by coloured fundus photography. Tetra-primer amplification refractory mutation system – polymerase chain reaction (T-ARMS-PCR) was used for genotyping. Serum sRAGE levels were measured by enzyme-linked immunosorbent assays (ELIZA).Results:The frequency of TT, TA and AA genotypes of rs1800624 polymorphism were: 92.7%, 6%, 1.3% in HC, 80%, 17.3%, 2.7% in DNR and 76.7%, 19.3%, 4.3% in DR groups. Heterozygous TA genotype and mutant A allele showed significant association with diabetes and DR vs HC. In dominant model, mutant allele showed significant association with DNR and DR vs HC. No significant association of rs1800624 was detected with DR and its sub-groups, non-proliferative DR (NPDR) and proliferative DR (PDR) vs DNR. Dividing NPDR into mild, moderate and severe, heterozygous TA genotype showed significant association with moderate and severe NPDR vs DNR. In DNR and DR groups, TA genotype was significantly associated with raised sRAGE.Conclusion:rs1800624 RAGE gene polymorphism might be a risk factor for T2DM and NPDR in Pakistani patients. Raised sRAGE levels have a positive correlation with PDR and are associated with heterozygosity of rs1800624 polymorphism in DNR and DR groups

Highlights

Diabetic individuals are at an increased risk of developing diabetic retinopathy (DR), the most frequent micro-vascular complication and a principal reason of vision-loss in adults
The total period of DM was significantly more in DR group vs diabetics with no retinopathy (DNR) group (13.02 ± 5.71 vs 9.31 ± 4.01 years)
According to chi-square test results, heterozygous TA genotype showed meaningful association with DM and DR vs healthy controls (HC) while homozygous TT was taken as reference

Summary

Introduction

Diabetic individuals are at an increased risk of developing diabetic retinopathy (DR), the most frequent micro-vascular complication and a principal reason of vision-loss in adults. Soluble RAGE (sRAGE) is an innately appearing inhibitor of RAGE mediated signalling pathways and may counteract its damaging effects by trapping RAGE ligands.3 374T/A (rs180024) RAGE gene polymorphism, positioned in the promoter region, causes upregulation of the RAGE and plays a fundamental role in the DR pathogenesis. It has been assessed for its association with DR in Asian, Caucasian, Indian, Malaysian and other populations.[2,4,5] Literature on the genetic factors involved in pathogenesis of DM and DR in Pakistani patients is very inadequate[6,7,8] and it is important to explore these factors to provide adequate and prompt therapy

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