Study of the role of tumor necrosis factor-α (-308 G/A) and interleukin-10 (-1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis.

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Abstract

Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications.

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Recent advances in the pathophysiology of ischemic acute renal failure.

M. Weinberg, Joseph V. Bonventre (2003)

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High-resolution DNA melting analysis for simple and efficient molecular diagnostics.

Gudrun H. Reed, Jana O. Kent, Carl T. Wittwer (2007)

High-resolution melting of DNA is a simple solution for genotyping, mutation scanning and sequence matching. The melting profile of a PCR product depends on its GC content, length, sequence and heterozygosity and is best monitored with saturating dyes that fluoresce in the presence of double-stranded DNA. Genotyping of most variants is possible by the melting temperature of the PCR products, while all variants can be genotyped with unlabeled probes. Mutation scanning and sequence matching depend on sequence differences that result in heteroduplexes that change the shape of the melting curve. High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid. Owing to its simplicity and speed, the method is a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.

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Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis.

P Woo, J Sillibourne, F E Crawley … (1999)

To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.