Polymorphisms of Aldose Reductase (ALR2) Regulatory Gene are Risk Factors for Diabetic Retinopathy in Type-2 Diabetes Mellitus Patients in Bali, Indonesia

Desak Made Wihandani1, *, Ketut Suastika2, I Nyoman Agus Bagiada1, Safarina G. Malik3
1 Department of Biochemistry, Faculty of Medicine, Udayana University, Jl. PB Sudirman, Denpasar 80232, Bali, Indonesia
2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Udayana University, Jl. PB Sudirman, and Sanglah Hospital, Jl. Kesehatan, Denpasar, Bali, Indonesia
3 Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia

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© 2018 Wihandani et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Biochemistry, Medical Faculty, Udayana University, Jl. PB Sudirman, Denpasar, Bali, Indonesia; Tel: +62 361 222510; Fax: +62 361 246656; E-mail:



The study aimed to elucidate whether the polymorphisms of the aldose reductase regulatory gene were risk factors for Diabetic Retinopathy (DR) in type-2 diabetes mellitus (T2DM) patients in Bali.


This is a case-control study including 35 cases of T2DM patients with DR paired with 35 cases with non-DR as controls. PCR analysis and DNA-sequencing were carried out to detect the C(-106)T and C(-12)G polymorphisms at the regulatory region of Aldose Reductase (ALR2) gene. Genotype and allele distributions were analyzed by Chi-squared test and independent t-and Mann-Whitney U tests were used to analyze other data.


Among all subjects in both groups, the baseline characteristics were homogenous except for systolic blood pressure, fasting blood glucose and 2-hours post-prandial blood glucose. This study found two polymorphisms, C(-104)T and C(-9)G, in the regulatory region of ALR2 gene. The result showed that the C(-104)T polymorphism was a risk factor for DR (OR=36; 95% CI = 4.43-292.85; p=0.001), but not the C(-9)G polymorphism (OR=1.28; 95% CI=0.48-3.38; p=0.621). Other findings in the study revealed that CC/CC haplotype is a protective factor for DR (OR=0.198; p=0.002), whereas CT/CC and CT/CG haplotypes as risk factors for DR with OR=15.58; p=0.002 and OR=2.29; p=0.005 respectively.


It can be concluded that C(-104)T polymorphism in the regulatory region of Aldose Reductase (ALR2) gene was the risk factor for DR among T2DM patients in Bali, Indonesia. However, small sample size, systolic blood pressure, fasting blood glucose and 2-hours post-prandial blood glucose could affect our finding.

Keywords: ALR2 gene, C(-104)T polymorphism, Diabetic retinopathy, Type-2 diabetes mellitus, C(-9)G polymorphism, PCR.