-429 T/C and -374 T/A Polymorphisms in Receptor Advanced Glycation Endproducts (RAGE) gene in Type 2 Diabetic Patients with Diabetic Retinopathy at the Dr. Sardjito General Hospital Yogyakarta

https://doi.org/10.22146/ijbiotech.7847

Agustina Welhelmina Djuma(1*), S. Sunarti(2), Pramudji Hastuti(3)

(1) Master Program of Basic Medical Science and Biomedicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(2) Department of Biochemistry, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(3) Politeknik Kesehatan Kementerian Kesehatan, Kupang, Indonesia
(*) Corresponding Author

Abstract


Receptor of advanced glycation endproduct (RAGE) plays an important role in the pathogenesis of diabetic vascular complications, such as diabetic retinopathy. The interaction between the RAGE and advanced glycation end product (AGE) leads to oxidative stress and could result in cellular activation and infl ammation. The production of AGE occurs normally during aging but it increases in hyperglycemia condition. The objective of this research was to investigate the association between -429 T/C and -374 T/A polymorphisms in RAGE gene with the risk of diabetic retinopathy (DR) of type 2 diabetic patients in Javanese population. This was a case control study which consisted of 40 type 2 diabetic patients with DR as case subjects and 40 type 2 diabetic patients without DR (NDR) as control subjects. Genotyping of polymorphism was performed by PCR-RFLP. Chi-square test and odds ratio models were used to evaluate the association of both polymorphisms and DR risk and to examine 2-SNP haplotype of -429 T/C and -374 T/A polymorphisms in RAGE gene on DR. The genotype frequencies of -429 T/C polymorphism in RAGE gene in DR subjects were TT = 72.5% and TC/CC = 27.5%; while in NDR subjects were TT = 80% and TC/ CC = 20%, with p = 0.431. The allele frequencies of -429 T/C polymorphism in DR subjects were T = 83.7% and C= 16.3%, while in NDR subjects were T = 87.5% and C = 12.5%, with p = 0.499. The genotype frequencies of -374T/A polymorphism in RAGE gene in DR subjects were TT = 67.5%, TA = 32.5% while in NDR subjects were TT =82.5%, TA = 17.5%, with p = 0.121. In DR subjects, the frequencies of T and A were 83.7% and16.3%, while in NDR subjects the frequencies of T and A were 91.2 % and 8.8%, with p = 0.151. Odds ratios of -429 T/C polymorphism were 1.52 (95% CI = 0.54 – 4.29) for TC/CC genotype and 1.358 (95% CI = 0.56 – 3.31) for C allele. Odds ratios of -374 T/A polymorphism were 2.27 (95% CI = 0.79 – 6.49) for TA genotype and 2.02 (95% CI = 0.76 – 5.37) for A allele. χ2-value for 2-SNP haplotype was p = 0.127. The -374 T/A polymorphism in RAGE gene was a stronger risk factor of DR than -429 T/C polymorphism in RAGE gene. There were not signifi cantly different of frequencies of genotypes, allele, and two-SNP haplotype of -429 T/C and -374 T/A polymorphisms in RAGE gene between DR subjects and NDR subjects.


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References

American Diabetes Association. 2007.
Diagnosis and classification of diabetes
mellitus. Diabetes Care, 30(1), S42-S47.


Bierhaus, A., Hofmann, M.A., Ziegler, R.,
and Nawroth, P.P., 1998. AGEs and
their interaction with AGE-receptors in
vascular disease and diabetes mellitus.
I. The AGE concept. Cardiovas. Res.,
37(3), 586-600.


Ciulla, T.A., Armando, G.A., and Bernard, Z.,
2003. Diabetic retinopathy and diabetic
macular edema. Diabetes Care, 26(9),
2653–2664.


Goldin, A., Beckman, J.A., Schmidt, A.M.,
and Creager, M.A., 2006. Advanced
glycation endproducts: sparking the
development of diabetic vascular
injury. Circulation, 114, 597-605.


Hudson, B.I., Stickland, M.H., Futers, T.S.,
and Grant, P.J., 2001. Effects of novel
polymorphisms in the RAGE gene on
transcriptional regulation and their
association with diabetic retinopathy.
Diabetes, 50,1505–1511.


Ilyas, S. 2006. Ikhtisar Ilmu Penyakit Mata.
Jakarta: Fakultas Kedokteran Universitas
Indonesia.


Liew, G., Klein, R., Wong, T.Y., 2009. The role
of genetics in susceptibility to diabetic
retinopathy. Int. Ophthalmol. Clin., 49(2),
35–52.


Lindholm, E., Bakhtadze, E., Sjogren, M.,
Cilio, C.M., Agardh, E., Groop, C.,
and Agardh, D., 2006. The -374 T/A
polymorphism in the gene encoding
RAGE is associated with diabetic
nephropathy and retinopathy in type
1 diabetic patients. Diabetologia, 49,
2745-2755.


Ramprasad, S., Radha, V., Mathias, R.A.,
Majumder, P.P., Rao, M.R.S., and
Rema, M., 2007. Rage gene promoter
polymorphisms and diabetic retinopathy
in a clinic-based population from South
India. Eye, 21, 395-401.


Rema, M., Saravanan, G., Deepa, R., and
Mohan, V., 2002. Familial clustering of
diabetic retinopathy in South Indian
Type 2 diabetic patients. Diabet. Med.,
19(11), 910-916.


Santos, I.C.R., Daga, D.R., Frigeri, H.R., Rea,
R.R., Almeida, A.C.R., Souza, E.M.,
Pedrosa, FO., Fadel-Picheth, CMT.,
and Picheth, G., 2010. The functional
polymorphisms -429 T>C and -374 T>A
of the RAGE gene promoter are not
associated with gestasional diabetes in
Euro-Brazilians. GMR, 9(2), 1130-1135.


Schmidt, A.M., Hori, O., Brett, J., Yan, S.D.,
Wautier, J.L., and Stern, D., 1994. Cellular
receptors for advanced glycation end
products. Implications for induction of
oxidant stress and cellular dysfunction
in the pathogenesis of vascular lesions.
Arterioscler. Thromb., 14, 1521-1528.


Sherwood, L. 2001. Fisiologi Manusia dari Sel
ke Sistem. Alih bahasa Pendit, B.U., Ed.
2. Jakarta : EGC.


Singh, R., Barden, A., Mori, T., and Beilin, L.,
2001. Advanced glycation end products:
a review. Diabetologia, 44,129–146.



DOI: https://doi.org/10.22146/ijbiotech.7847

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