Abstract
Background: Chronic kidney disease (CKD) is a condition associated with progressive loss of kidney function and kidney damage. The two common causes of CKD are diabetes mellitus and hypertension. Other causes of CKD also include polycystic kidney disease, obstructive uropathy and primary glomerulonephritis. The receptor for advanced glycation end-products (RAGE) is a multi-ligand cell surface receptor of the immunoglobulin superfamily and it has been associated with kidney disease in both non-diabetic and diabetic patients. Presently, data on the association between RAGE polymorphisms and CKD in the Malaysian population is limited, while numerous studies have reported associations of RAGE polymorphisms with diabetic complications in other populations. The present study aims to explore the possibility of using RAGE polymorphisms as candidate markers of CKD in Malaysian population by using association analysis.Methods: A total of 102 non-diabetic CKD patients, 204 diabetic CKD patients and 345 healthy controls were enrolled in the study. DNA isolated from blood samples were subjected to genotyping of RAGE G82S, −374T/A, −429T/C, 1704G/T and 2184A/G polymorphisms using real-time polymerase chain reaction (PCR). The 63-bp deletion, a polymorphism in the RAGE gene promoter, was genotyped using conventional PCR method and visualized using agarose gel electrophoresis. The collective frequencies of genotypes with at least one copy of the minor alleles of the four polymorphisms were compared between the non-diabetic CKD patients, diabetic CKD patients and healthy controls.Results: After adjustment of age, gender and ethnic groups in binary logistic regression analysis, the G82S CT + TT genotypes were associated with non-diabetic CKD patients when compared with diabetic CKD patients (p = 0.015, OR = 1.896, 95% CI = 1.132–3.176). After further adjustment of CKD comorbidities, the G82S CT + TT genotypes were still associated with non-diabetic CKD patients when compared with diabetic CKD patients (p = 0.011, OR = 2.024, 95% CI = 1.178–3.476). However, it cannot be suggested that G82S polymorphism was associated with CKD in non-diabetic patients in this study. This is because there were no significant differences in the frequencies of G82S CT + TT genotypes between non-diabetic CKD patients and healthy controls. In addition, the RAGE −374T/A, −429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms were also not associated with non-diabetic CKD patients and diabetic CKD patients in this study.Conclusion: The G82S, −374T/A, −429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms examined in this study were not associated with chronic kidney disease in the Malaysian patients.
Highlights
Chronic kidney disease (CKD) is a general term for heterogeneous renal disorders which is characterized by progressive kidney damage and estimated glomerular filtration rate of less than 60 ml/min/1.73 m2 for three months or more (Levey et al, 2003; Stevens & Levey, 2009)
Given the associations of several receptor for advanced glycation end-products (RAGE) polymorphisms with kidney diseases in the published literature, the present study aims to explore the possibility of using RAGE polymorphisms as candidate markers of CKD in Malaysian population by using
This study investigates the G82S, -374T/A, -429T/C, 1704G/T, 2184A/G and 63-bp deletion polymorphisms based on their effects on RAGE expression and function which potentially affect CKD pathogenesis: (i) G82S polymorphism is a missense mutation in exon 3 of the RAGE gene which potentially regulates RAGE function (Kalea, Schmidt & Hudson, 2009), (ii) the polymorphisms in the transcriptional start site of RAGE such as -374T/A, -429T/C and 63-bp deletion polymorphisms regulate the transcription of RAGE (Hudson et al, 2001), and (iii) the 1704G/T polymorphism and 2184A/G polymorphism may be responsible for alternative splicing that produces endogenous secretory RAGE which is cytoprotective against RAGE ligands (Yonekura et al, 2003; Schlueter et al, 2003)
Summary
Chronic kidney disease (CKD) is a general term for heterogeneous renal disorders which is characterized by progressive kidney damage and estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2 for three months or more (Levey et al, 2003; Stevens & Levey, 2009). The two common causes of kidney failure in Malaysia are diabetes mellitus and hypertension, with other causes being polycystic kidney disease, obstructive uropathy and chronic glomerulonephritis (National Renal Registry, 2014). The receptor for advanced glycation end-products (RAGE) is a multi-ligand cell surface receptor of the immunoglobulin superfamily and it has been associated with kidney disease in both non-diabetic and diabetic patients. It cannot be suggested that G82S polymorphism was associated with CKD in non-diabetic patients in this study This is because there were no significant differences in the frequencies of G82S CT + TT genotypes between non-diabetic CKD patients and healthy controls. The RAGE -374T/A, How to cite this article Wong et al (2016), Association of the receptor for advanced glycation end-products (RAGE) gene polymorphisms in Malaysian patients with chronic kidney disease.
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