A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression

Suehiro, Tadashi; Nakamura, Toshihiro; Inoue, Mari; Shiinoki, Tomoko; Ikeda, Yukio; Kumon, Yoshitaka; Shindo, Masanori; Tanaka, Hideo; Hashimoto, Kozo

doi:10.1016/s0021-9150(99)00379-2

Cited by 148 publications

(102 citation statements)

References 15 publications

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“…In this investigation, we found that the L and M allele frequencies for the PON1 coding-region (L55M) polymorphism were similar to those of Japanese and Chinese populations who displayed very low frequencies of the M allele (M = 0.06) (Zama et al 1997;Sanghera et al 1998;Cao et al 1998;Suehiro et al 2000), but these results were different from those of Asian Indian and Caucasian populations (M = 0.36) (Brophy et al 2001;Leviev and James 2000;Ferre et al 2002). However, differences in Q and R allele frequencies for the PON1 Q192R polymorphism between this population (Q = 0.71, R = 0.29) and Japanese population (Q = 0.40, R = 0.60) were observed, but were not found when compared with those of Caucasian populations (Q = 0.74, R = 0.26) (Zama et al 1997;Brophy et al 2001;Suehiro et al 2000).…”

Section: Discussionmentioning

confidence: 51%

“…However, differences in Q and R allele frequencies for the PON1 Q192R polymorphism between this population (Q = 0.71, R = 0.29) and Japanese population (Q = 0.40, R = 0.60) were observed, but were not found when compared with those of Caucasian populations (Q = 0.74, R = 0.26) (Zama et al 1997;Brophy et al 2001;Suehiro et al 2000). The very low frequency of the 55 M genotype in the Thai population was surprising, however, in a recent study of Han Chinese, no polymorphism of this site was found (Wang et al 2003), further investigations in this area are required.…”

Section: Discussionmentioning

confidence: 56%

“…These polymorphisms are at position À108 (T or C), À162 (A or G) and À909 (G or C) where the base immediately before the start codon is numbered as ''À1'' (Brophy et al 2001;Suehiro et al 2000;Leviev and James 2000). In addition, the three regulatory and the two coding polymorphisms all show significant linkage disequilibrium (LD) to each other (Brophy et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Paraoxonase 1 status in the Thai population

et al. 2005

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Human serum paraoxonase 1 (PON1), a highdensity lipoprotein (HDL)-associated enzyme, has been shown to reduce the oxidation of low-density lipoprotein (LDL) and HDL by degrading lipid peroxides. This property of PON1 accounts for its ability to protect against atherosclerosis. In this study, we identified four polymorphisms in both the coding (L55M and Q192R) and regulatory regions (T-108C and G-909C) of the human PON1 gene in 202 healthy Thai individuals and investigated the influence of these polymorphisms on serum PON1 activity towards three substrates, namely, paraoxon, phenylacetate and diazoxon. The PON1 L55M, Q192R and G-909C polymorphisms significantly affected the variation in serum PON1 activity towards paraoxon. Serum PON1 activity towards paraoxon was significantly different among the genotype groups, as follows: 55LL > 55LM/55MM, 192RR > 192QR > 192QQ and À909CC > À909CG > À909GG. The PON1 Q192R and G-909C polymorphisms also influenced the variation in serum PON1 activity towards diazoxon but in the opposite direction to the activity towards paraoxon. Only the PON1 L55M polymorphism was associated with significant variation in serum PON1 activity towards phenylacetate while the PON1 T-108C polymorphism had no significant effect on serum PON1 activity towards any substrate. We also found linkage disequilibrium among the polymorphic sites, including Q192R versus L55M, Q192R versus T-108C and Q192R versus G-909C. Serum PON1 activity towards both paraoxon and phenylacetate, but not diazoxon, was positively correlated with HDL cholesterol (HDL-C) and apo AI concentrations. None of the PON1 polymorphisms significantly affected serum lipid, lipoprotein or apolipoprotein concentrations. Our findings suggest that the physiological relevance of the PON1 polymorphisms is that they are associated with significant differences in serum PON1 activity, and the impact of PON1 polymorphisms on this activity is substrate-dependent.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Paraoxonase 1 status in the Thai population

et al. 2005

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“…We previously reported that pitavastatin enhanced the promoter activity of PON1 gene in HepG2 cells using a reporter gene assay method and that we could detect PON1 mRNA but not PON1 protein in HepG2 cells [22]. Huh7 is another human hepatoma cell line and expresses PON1 protein.…”

Section: Effects Of Pitavastatin On Pon1 Promoter Activity and Pon1 Pmentioning

confidence: 92%

“…We used plasmid constructs with PON1 gene 5'-flanking regions for luciferase assay, as reported previously [22]. pGL3 luciferase reporter vectors (Promega) introduced DNA fragments of PON1 genes (-587/-6) (pGL3-PON1[587/-6]) were used in the present study.…”

Section: Plasmid Constructs and Transfectionmentioning

confidence: 99%