SNPs in adipokines - adiponectin and leptin - as risk factors for diabetic complications: evidence for a "double-hit" mechanism?
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| Year of publication | 2007 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Diabetic angiopathy is now recognized as an inflammatory process of the vessel wall. Type 2 diabetes (T2DM) is far the most common type frequently accompanied by obesity in affected subjects. Co-occurrence of both diseases is not just an epidemiological association but a likely consequence of common ethiopathogenesis. Adipokines too play multiple roles in inflammation ultimately activating, similarly to hyperglycemia itself, transcription factor NFkB with subsequent inflammatory changes in vascular tissue. Leptin (LEP) and adiponectin (APM1) are, apart of their role in energy homeostasis, examples of vascular pro- and anti-inflammatory mediators, respectively. Genetic variability in the APM1 and LEP genes could not only modulate the risk of obesity and/or T2DM but also influence susceptibility to the development of diabetic complications. The aim was (i) to analyse association between common functional SNPs APM1 94T/G and LEP -2548G/A with diabetic nephropathy in the pilot study and (ii) using additional more densely spaced SNPs in both genes to ascertain event. haplotype association (ongoing). The cross-sectional study comprised 331 T2DM patients with normoalbuminuria (n=146, age 59.5 +/-14.6 yrs) or diabetic nephropathy (n=185, age 65.2 +/-14.6 yrs). Genotypes of APM1 94T/G and LEP -2548G/A were detected by PCR-based methodology. Allele frequencies of the two SNPs did not differ significantly (P>0.05, chi-square test), nevertheless, both SNPs exhibited statistically significant deviations from Hardy-Weinberg equilibrium in the nephropathy group (P<0.05, chi-square test). Preliminary results indicate that carriers of certain variants in APM1 and LEP genes might be susceptible to diabetic nephropathy. Results of ongoing haplotype analysis will be thus very informative. |
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