Vascular endothelial growth factor gene polymorphisms in North Indian patients with end stage renal disease

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• 作者：Swayam Prakash^a ; Narayan Prasad^b ; Raj K. Sharma^b ; Rehan M. Faridi^a ; Suraksha Agrawal^a ; ^{suraksha@sgpgi.ac.in} ; ^{sur_ksha_agrawal@yahoo.co.in}
• 关键词：End stage renal disease (ESRD) ; Single Nucleotide Polymorphism (SNP) ; Vascular endothelial growth factor (VEGF)
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：May, 2012
• 卷：58
• 期：2
• 页码：261-266
• 文件大小：307 K

摘要

Context

Vascular endothelial growth factor (VEGF) is involved in the development and differentiation of the vascular system. VEGF is expressed constitutively by epithelial cells from embryonic to adult kidneys and may play a key role in progression of kidney diseases. It is required for the growth and proliferation of glomerular and peritubular endothelial cells. In the kidney VEGF expression is prominently found in glomerular podocytes and in tubular epithelial cells, while VEGF receptors are mainly seen on preglomerular, glomerular, and peritubular endothelial cells.

Objectives

We have investigated the role of VEGF gene polymorphisms (鈭?578C/A,鈭?549 18 bp I/D, 鈭?154 G/A and +936 C/T) as a susceptibility marker for end stage renal disease (ESRD).

Participants and methods

We genotyped VEGF gene polymorphism in three hundred patients and three hundred and fifty ethnically matched unrelated healthy controls free from any renal disease. These markers were studied using ARMS-PCR and PCR-RFLP methods. Patients were categorized on the basis of the histo-pathological subtypes into chronic glomerulonephritis (CGN = 109), hypertensive nephrosclerosis (HTN = 106) and chronic interstitial nephritis (CIN = 60).

Results

VEGF 鈭?578C and 鈭?549D alleles were found to be ESRD causative alleles. It was observed that there was significant differences in the frequencies of the T allele of +936C/T polymorphism among CGN, HTN and CIN respectively. VEGF 鈭?154AA genotype and A allele were associated significantly with CGN. T-G-A-D, T-A-C-I,C-G-A-D,C-A-C-D,C-G-C-I,C-A-A-D and T-G-C-D were seven haplotypes concurred in all the ESRD patients irrespective of underlying disease. While C-G-C-D & C-G-A-I haplotypes showed risk association in CGN & CIN, C-A-C-I was observed to play predisposing role in HTN.

Conclusion

The results highlight the role of studied VEGF polymorphisms in end stage renal disease at large and subsequently in the three primary kidney diseases among the North Indian population.