Endocrine Abstracts

Aim: To assess the association of the endothelial dysfunction (ED) parameters and the lipid-lowering response to atorvastatin therapy in patients with T2D with genetic markers of inflammation.

Methods: We include 97 T2D patients with first prescribed atorvastatin 10–20 mg: M/F 26/71; mean age 57 years. After 12 month of statin therapy, patients had fasting lipid profiles and ED parameters repeated. For ED evaluation, we performed pulse wave analysis with reactive hyperemia by peripheral arterial tonometry. The genotypes were identified by PCR in real time with the TaqMan probes for a complex of polymorphic markers. Statistic analysis was evaluated using the Mann-Whitney, Wilcoxon tests, P<0.05.

Results: There was no difference in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels and ED parameters between the genotypes of studied genes in statin-untreated subjects. With statin therapy, PPARG2Pro/Pro had significantly TC, LDL-C lowering compared with PPARG2Pro/Ala, PPARG2 Ala/Ala patients (for TC: 20.74% vs 4.6% and 5.61%; P=0.04, respectively; for LDL-C: 26.00% vs 6.11% and 7.32%; P=0.029, respectively). The carries GG of TNFα G(238)A and GA of TNFα G(308)A had significantly greater in amplitude of postocclusive wave increase (Apw) compared with the carries GA of TNFα G(238)A and GG of TNFα G(308)A (+8.16% vs −0.93%, P=0.04;+44% vs −4.4%, P=0.004, respectively). The percentage of Apw and TC, LDL-C improvement did not depend on age, diabetes duration, basal lipids levels and HbA1c but it depend on genotypes distribution of TNF-a G(238)A and G(308)A and PPARG2 Pro12Ala, respectively. There was no statistically significant association between ED and atorvastatin response with other studied markers.

Conclusion: PPARG2 Pro12Ala polymorphism accounts for interindividual variability of response to statin therapy in patients with ?2D. Significant association of TNF-α gene polymorphism with ED in T2D suggests an important role of inflammation in the genesis of MVD.