Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification

作者: Bharti Mackness , Michael I Mackness , Sharon Arrol , Wajdi Turkie , Paul N Durrington

DOI: 10.1016/S0014-5793(98)00064-7

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摘要: Human serum paraoxonase (PON1) associated with high density lipoprotein (HDL) has been postulated to have a role in protecting low (LDL) against oxidative modification, which led the proposal that PON1 is an anti-atherogenic, anti-inflammatory enzyme. two genetically determined polymorphic sites giving rise amino-acid substitutions at positions 55 (L→M) and 192 (R→Q) therefore 4 potential alloenzymes. We examined effects of these molecular polymorphisms on ability HDL protect LDL from modification. protected whatever combination alloenzymes present it. However, QQ/MM homozygotes was most effective while RR/LL least effective. Thus after 6 h co-incubation Cu2+ PON1-QQ retained 57±6.3% its original PON1-QR less 25.1±4.5% (P<0.01) PON1-RR only 0.75±0.40% (P<0.005). In similar experiments LL LM genotypes 21.8±7.5% 29.5±6.6% (P=NS), respectively, their protective ability, whereas PON1-MM maintained 49.5±5.3% (P<0.01). may affect impede development atherosclerosis prevent inflammation.

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