Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients

Abstract

Background: Data from previous studies on the role of inflammatory cytokines as biomarkers for diabetic kidney disease (DKD) are contradictory. The association of a particular inflammatory cytokine single nucleotide polymorphism (SNP) with susceptibility to DKD has not been consistently replicated. We aimed to investigate the utility of inflammatory cytokines as biomarkers for DKD in type 2 diabetes mellitus (T2DM) patients. Association of inflammatory cytokine gene SNPs with the development of DKD was also explored.

Subjects and Methods: One hundred and fifty-nine Kuwaiti subjects were recruited in this study, including 50 T2DM patients without DKD, 67 diabetic DKD patients and 42 healthy subjects. Plasma levels of interleukin-6 (IL-6), IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were measured by enzyme-linked immunosorbent assays. Nine SNPs, including 2 SNPs in IL-6, 3 SNPs in IL-10, 1 SNP in IFN-γ and 3 SNPs in TNF-α, were genotyped using TaqMan SNP genotyping assays.

Results: Diabetic DKD patients showed higher IL-6, IL-10, IFN-γ and TNF-α levels than those without DKD. Diabetic DKD patients had a significantly higher frequency of IL-10 − 1082 A allele than those without DKD (p = 0.001). No significant association of IL-6 − 174/−597 haplotypes with DKD risk was detected (p = 0.188). Distribution of IL-10 − 592/−819/−1082 haplotypes differ significantly between T2DM patients with/without DKD (p = 0.014). Diabetic DKD patients had a significantly lower frequency of IL-10 − 592C/−819C/−1082G haplotype than those without DKD (p = 0.002).

Conclusions: Although inflammatory cytokine genotypes and, more importantly, haplotypes may have the potential to identify those patients at risk of DKD, hence, improving DKD predisposition prediction, further investigations regarding their real clinical significance is warranted in a large cohort of patients.

Keywords:

• Type 2 diabetes mellitus
• diabetic kidney disease
• cytokines
• single nucleotide polymorphisms

Ethical approval

All procedures performed were in accordance with the ethical standards of the Dasman Diabetes Institute, Kuwait city, Kuwait and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclosure statement

No potential conflict of interest was reported by the authors.