THE ASSOCIATIONS OF PON1 AND APOE POLYMORPHISMS WITH PLASMA LIPID LEVELS AND THE RISK FOR LATE COMPLICATIONS IN TYPE 2 DIABETES PATIENTS.

Background: Besides good glycemic control, also control of lipid levels can effectively prevent or delay late type 2 diabetes (T2D) complications. As apolipoprotein E (APOE) and paraoxonase 1 (PON1) were shown to suppress atherosclerosis, we investigated the associations of common functional PON1 and APOE polymorphisms with plasma lipid levels and the risk for late complications in T2D patients. Methods: Our retrospective genetic association study included 181 T2D patients genotyped for PON1 rs622, PON1 rs854560, APOE rs429358 and APOE rs7412. Results: PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.024) and lower LDL/HDL ratio (p=0.031) under recessive model. Also in the subgroup of statin treated patients, PON1 rs622 G allele carriers had significantly lower LDL-C (p=0.019), lower total cholesterol/LDL ratio (0.043) and lower LDL/HDL ratio (0.009) when compared to noncarriers. After adjustment for clinical characteristics only associations of PON1 rs622 with macrovascular complications (p=0.002) and MI (p=0.041) remained significant. PON1 rs854560 and APOE genotypes were not associated with late T2D complications. Conclusion: Although our data show some associations between PON1 polymorphisms and lipid levels in T2D patients, as well as with late T2D complications, these associations do not seem to be clinically relevant in T2D patients. [ABSTRACT FROM AUTHOR]

Uvod: Ftored dobre kontrole glikemije, kontrola nivoa lipida može efikasno sprečiti ili odložiti kasne komplikacije dijabetesa tipa 2 (T2D). Kako se pokazalo da apolipoprotein E (APOE) i paraoksonaza 1 (PON1) suzbijaju aterosklerozu, istražili smo povezanost uobičajenih funkcionalnih polimor- fizama PON1 i APOE sa nivoima lipida u plazmi i rizikom od kasnih komplikacija kod pacijenata sa T2D. Metode: Naša retrospektivna studija genetičke asocijacije uključila je 181 pacijenta sa T2D genotipiziranim za PON1 rs622, PON1 rs854560, APOE rs429358 i APOE rs7412. Rezultati: Nosioci alela PON1 rs622 G imali su značajno niži LDL-C (p=0,024) i niži odnos LDL/HDL (p=0,031) pod recesivnim modelom. Ta kode u podgrupi pacijenata lečenih statinima, nosioci alela PON1 rs622 G imali su značajno niži LDL-C (p=0,019), niži odnos ukupnog holesterola/LDL (0,043) i niži odnos LDL/HDL (0,009) u poređenju sa onima koji nisu nosioci. Nakon prilagođavanja kliničkih karakteristika, ostala je značajna samo povezanost PON1 rs622 sa makrovaskularnim komplikacijama (p= 0,002) i IM (p= 0,041). Genotipovi PON1 rs854560 i APOE nisu bili povezani sa kasnim komplikacijama T2D. Zaključale lako naši podaci pokazuju neke povezanosti između polimorfizma PON1 i nivoa lipida kod pacijenata sa T2D, kao i sa kasnim komplikacijama T2D, čini se da ove veze nisu klinički relevantne kod pacijenata sa T2D. [ABSTRACT FROM AUTHOR]