APO A2 -265T/C Polymorphism Is Associated with Increased Inflammatory Responses in Patients with Type 2 Diabetes Mellitus

Abstract

BackgroundApolipoprotein A2 (APO A2) is the second most abundant structural apolipoprotein in high density lipoprotein. Several studies have examined the possible effect of APO A2 on atherosclerosis incidence. Due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between APO A2 -265T/C polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (T2DM) patients.MethodsIn total, 180 T2DM patients, with known APO A2 -265T/C polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. Dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 [PTX3], high-sensitivity C-reactive protein [hs-CRP], and interleukin 18) were measured. The data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance.ResultsAfter adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the CC genotype showed higher hs-CRP (P=0.001, P=0.008, and P=0.01, respectively) and lower PTX3 (P=0.01, P=0.03, and P=0.04, respectively) in comparison with the T allele carriers. In the patients with the CC genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. However, regarding the T allele carriers, the plasma hs-CRP level was significantly higher in the obese patients compared to the non-obese patients (P=0.01).ConclusionIn the T2DM patients, the CC genotype could be considered as a risk factor and the T allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. Our results confirmed the anti-atherogenic effect of APO A2, though more studies are required to establish this effect.

Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure

“…Some studies have shown that overexpression of ApoA-II could confer pro-inflammatory properties to HDL by reducing protection against LDL oxidation and stimulating lipid hyperoxidation and monocyte transmigration in mice 34 and that ApoA-II may maintain host responses to lipopolysaccharide (LPS) by suppressing inhibitory activity of LPS binding protein 35 . In contrast, other studies have suggested an anti-inflammatory effect of ApoA-II in humans 36 . Macrophages and monocytes activated by inflammation may cleave the C-terminal part of SAA and induce AA amyloid fibril formation 37 .…”

Prenatal Exposure to Lipopolysaccharide Induces PTX3 Expression and Results in Obesity in Mouse Offspring

“…Glucose metabolism tests were measured to demonstrate obesity-induced glucose metabolism disorder [ 33 , 34 ]. The fasting blood glucose of the all-of-weeks-age mice in the LPS group had modicum increased, but there was no significant difference.…”

“…Furthermore, previous studies have demonstrated that inflammatory factor PTX3 plays an important role in both inflammation and obesity by previously reported literature [ 34 ]. Correlation analysis showed that LPS could induce PTX3 expression in macrophage cells by activating the transcription factor NF-κB induction [ 35 ].…”

A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome

“…A nutrigenetic interaction with omega 3 PUFA supplementation in the modulation of plasma CRP has been observed [ 31 ]; and associated with insulin resistance, higher levels of inflammatory metabolites in plasma [ 32 ], and other age-related alterations [ 33 ]. Rs5082, located in the promoter region of apolipoprotein A2 ( APOA2 ) gene, has been shown to interact with dietary fatty acid intake to modulate inflammation [ 34 , 35 ], and is associated with both lower transcription rate and lower concentration of Apolipoprotein A-II in plasma [ 36 ], conferring higher risk of obesity and diabetes mellitus [ 37 , 38 ]. Furthermore, non-T subjects with high omega 3 PUFA intake show greater capacity for oxidative stress neutralization, whereas T carriers have been associated with resistance to increase superoxide dismutase 2 (SOD2) activity with omega 3 PUFA intake [ 39 ] and also with an increase in plasma oxidative biomarkers when they present a rich omega 6 PUFA diet [ 39 ].…”