Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians.

Abstract

OBJECTIVE:

Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the -420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans.

DESIGN AND METHODS:

We examined the association of three resistin polymorphisms, -852A>G, -420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851).

RESULTS:

Resistin levels were higher, dose-dependently, with the -420G allele (CC 5.9 +/- 2.7 ng/ml, GC 6.5 +/- 4.0 ng/ml and GG 7.2 +/- 4.8 ng/ml, trend P = 0.04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1.07 (1.00-1.15), P < 0.05)]. The -852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1.06 (95% CI 1.01-1.11), P = 0.01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0.04) and the AGT haplotype was related to CRP (P = 0.04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores.

CONCLUSIONS:

Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.

• Authors: Atif N Qasim, Thomas S Metkus, Mahlet Tadesse, Michael Lehrke, Stephanie Restine, Megan L Wolfe, Sridhar Hannenhalli, Thomas Cappola, Daniel J Rader, Muredach P Reilly
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 70 Issue 5 Pg. 698-705 (May 2009) ISSN: 1365-2265 [Electronic] England
• PMID: 18710472 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adipokines
• Biomarkers
• Cytokines
• Inflammation Mediators
• RETN protein, human
• Resistin

Topics

• Adipokines (blood)
• Adiposity (genetics)
• Adult
• Biomarkers (blood)
• Coronary Artery Disease (blood, complications, genetics)
• Cytokines (blood)
• Female
• Gene Frequency
• Genetic Variation
• Haplotypes
• Humans
• Inflammation (blood, complications, genetics)
• Inflammation Mediators (blood)
• Linkage Disequilibrium
• Male
• Metabolic Syndrome (blood, complications, genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Resistin (genetics)
• White People