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Tumor necrosis factor alpha gene polymorphisms and haplotypes in Egyptian children with nephrotic syndrome

Cytokine, ISSN: 1043-4666, Vol: 102, Page: 76-82
2018
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Article Description

Nephrotic syndrome (NS) characterized by complex pathogenesis and clinical course with relapses; and needs novel breakthroughs for decades. Polymorphisms of cytokines genes including tumor necrosis factor alpha ( TNF-α ) may influence susceptibility to NS as well as different patients' steroid responses. In the current study, we demonstrated the potential roles of TNF-α promoter gene polymorphisms [−238, −308, −863] and haplotypes in susceptibility to childhood NS. Also, elucidating their possible influence on patients' steroid response and serum TNF-α level. This case-control study included 150 children suffering from NS and 150 healthy children. Polymerase chain reaction- restriction-fragment length polymorphism (PCR-RFLP) was performed to evaluate different TNF-α gene polymorphism. TNF-α serum levels were assessed by ELISA. Serum TNF-α levels were significantly higher in NS patients than in controls and in steroid resistant NS (SRNS) than in steroid sensitive NS (SSNS) (P < 0.001 for each). The risk of NS in patients carrying TNF-α- 238 GA genotype, and TNF-α- 308 GA or AA genotypes and allele A was significantly increased compared to healthy children. While no significant association was detected between TNF-α-863 and NS. The risk of resistance to steroid therapy was significantly high in NS carrying TNF-α-238 GA genotype and A allele, TNF-α-308, AA genotypes and A allele, and TNF-α -863 CA, AA genotypes and A allele. The TNF-α GCG (−308/−863/−238) haplotype has protective roles against NS and steroid resistance. However, the risk of NS was significantly high in TNF-α AAG and AAA haplotype's carriers compared to healthy children. Additionally the risk of steroid resistance was significantly high in TNF-α AAA haplotype's NS carrier (OR (95%CI): 2.2 (1.19–4.36), P = 0.01). Moreover, we found significant higher serum TNF-α levels NS patients including SSNS and SRNS carrying mutant allele TNF-α -238 GA genotype, −308 GA and AA and −863 CA and AA wild genotype's carriers than in those GG, GG and CC respectively. Interstingely, TNF-α levels were significantly higher in healthy children carrying TNF -α(−308/−863/−238) [AAG and AAA haplotypes], NS cases carrying [ACA, AAG, AAA haplotypes], and in SSNS carrying [ACA and AAA haplotypes] than in those carrying GCG, haplotype of wild alleles. This study reported, for the first time, that TNF -α promoter gene polymorphisms and/or haplotypes are risk factors of NS and resistance to steroid among Egyptian children.

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