9.4. PON1 polymorphisms in humansSt

9.4. PON1 polymorphisms in humans
Studies indicate that plasma paraoxonase activity inhumans exhibits a polymorphic distribution, with indi-viduals showing a trimodal pattern with either high,intermediate or low paraoxonase activity. Gene frequen-cies for high or low metabolizers have also been shownto vary among groups of different ethnic or geograph-ical origins (Costa et al., 2002). The molecular basisof the polymorphism has been associated with severalmutations (Brophy et al., 2001). It should be noted thatin a given population, plasma PON1 activity can varyup to 40-fold (Mueller et al., 1983; Davies et al., 1996;Richter and Furlong, 1999), and differences in PON1protein levels up to 13-fold are also present within asingle PON1192genotype (Furlong et al., 2002; Costaet al., 2003a,b). Measurement of an individual’s PON1plasma activity takes into account all polymorphismsthat might affect activity (Costa et al., 2005). Thisis accomplished through the use of a high-throughputenzyme assay involving two PON1 substrates (usuallydiazoxon and paraoxon) (Furlong et al., 2002; Josse etal., 1999). Thus, a multiplex assay could help to identifyputative PON1 polymorphic activity in conjunction with diagnosing liver injury. Because of polymorphisms, theutility of PON1 activity appears to be greater for pre-clinical evaluation of hepatotoxicity compared to use inthe clinic. Nevertheless, multiplexing technology wouldenable reduced PON1 values to reflect either liver tox-icity or polymorphisms without having to profile thegenomes of clinical trial participants

Results (Indonesian) 2:

9.4. Polimorfisme PON1 pada manusia
Studi menunjukkan bahwa aktivitas paraoxonase plasma inhumans menunjukkan distribusi polimorfik, dengan indi-individu-menunjukkan pola trimodal dengan baik tinggi, menengah atau rendah aktivitas paraoxonase. Gen frequen-badan-untuk metabolisme tinggi atau rendah juga telah shownto bervariasi antara kelompok etnis atau geograph-ical yang berbeda (Costa et al., 2002). The basisof molekul polimorfisme yang telah dikaitkan dengan severalmutations (Brophy et al., 2001). Perlu dicatat thatin populasi tertentu, aktivitas PON1 plasma dapat varyup sampai 40 kali lipat (Mueller et al, 1983;. Davies et al, 1996;. Richter dan Furlong, 1999), dan perbedaan tingkat PON1protein hingga 13 kali lipat juga hadir dalam asingle PON1192genotype (Furlong et al, 2002;.. Costaet al, 2003a, b). Pengukuran aktivitas PON1plasma individu memperhitungkan semua polymorphismsthat mungkin mempengaruhi aktivitas (Costa et al., 2005). Iniadalah dicapai melalui penggunaan alat tes tinggi throughputenzyme melibatkan dua substrat PON1 (usuallydiazoxon dan paraoxon) (Furlong et al, 2002;. Josse dkk, 1999.). Dengan demikian, assay multipleks bisa membantu identifyputative PON1 aktivitas polimorfik dalam hubungannya dengan mendiagnosis kerusakan hati. Karena polimorfisme, theutility aktivitas PON1 tampaknya lebih besar untuk evaluasi pra-klinis hepatotoksisitas dibandingkan dengan menggunakan inthe klinik. Namun demikian, teknologi multiplexing wouldenable dikurangi nilai PON1 untuk mencerminkan baik hati tox-I-City atau polimorfisme tanpa harus pro fi le thegenomes peserta uji klinis