An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients

Abstract

The human chromosome 7p21 locus harbors a major gene that influences variation of glomerular filtration rate and development of end-stage renal disease. The pro-inflammatory IL-6 cytokine is a candidate gene since chronic inflammation has been implicated in diabetic nephropathy and this gene is located under the peak of linkage. To test this, single nucleotide polymorphism (SNP) and haplotype analyses were performed using a case-control study of 295 patients consisting of 138 with proteinuria, 157 with chronic renal failure and these were compared to 174 control patients with normal albumin excretion. Five tagging SNPs were selected for analysis based on linkage disequilibrium patterns and proximity to the functionally important -634G>C SNP in the IL-6 promoter. Initial analysis suggested that a -174G>C polymorphism may be associated with risk of chronic renal failure but this was not significant after Bonferroni correction. While haplotype analyses showed no association with proteinuria; a significant association with chronic renal failure was found. There was significantly more of the GGGAGC haplotype among patients with chronic renal failure compared to controls and this association remained significant even after correction for multiple testing. Our study has found a specific IL-6 haplotype conferring risk for impaired renal function in patients with type 2 diabetes.

Evaluation of Five Interleukin Genes for Association with End-Stage Renal Disease in White Europeans

“…1). SNPs rs1800797 [9], rs1800871 [12], rs16347 [13], rs151672 [13] and rs1800796 [14] were also selected for genotyping as they had previously been found to have been associated with ESRD. All SNPs were genotyped using MassARRAY® iPLEX® Gold (Sequenom, San Diego, Calif., USA) and genotypes called using MassARRAY TYPER Analyzer (Version 3.4.0, Sequenom).…”

“…Mutations within the IL1 gene cluster have been associated with kidney disease [7]. IL6 levels are elevated in many patients with ESRD [8] and the IL6 gene resides in a chromosome region associated with impaired renal function [9]. The regulatory protein, IL10, appears to suppress chemokine release and has been shown to reduce inflammation in a rodent model of chronic kidney disease [10].…”

Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population

“…El rs2069843 está en una región génica con alto grado de desequilibrio de ligamiento (41). En estudios recientes se ha demostrado el alto grado de desequilibrio de ligamiento entre los polimorfismos sinténicos rs2069843 y rs2069845, cuyas variantes se heredan como haplotipos en el mismo gen (IL6) en poblaciones con un importante componente genético africano como la brasileña (42).…”

Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease

“…Варианты генов цитокинов отличают больных СД-2 от общей популяции [32]. Выявлены взаимосвязи развития ДН у больных СД-2 и вариантами генов IL-6 174 G/C [33,34].…”