scholarly journals Distribution of paraoxonase 1 coding region polymorphisms in Serbian population

Genetika ◽  
2010 ◽  
Vol 42 (2) ◽  
pp. 235-247 ◽  
Author(s):  
I. Pejin-Grubisa ◽  
I. Buzadzic ◽  
B. Jankovic-Orescanin ◽  
N. Barjaktarovic-Vucinic

Serum paraoxonase 1 (PON1) in humans is a protein component of high-density lipoprotein (HDL) particles that protects against oxidative damage, detoxifies toxic metabolites of organophosphorus pesticides and nerve agents and activates or inactivates specific drugs. It has been reported that PON1 gene coding region polymorphisms, L55M and Q192R, could influence both expression level and catalytic activity of PON1, and their link with a broad spectrum of diseases has been described. The aim of this study was to determine the frequencies of PON1 coding region polymorphisms Q192R and L55M in Serbian population. The most frequent alleles were Q (0.77) for Q192R and L (0.68) for L55M. Genotypes QQ (0.60) and LL (0.47) and combined genotype QQ/LL (0.26) were the most frequent in examined population.

2007 ◽  
Vol 58 (3) ◽  
pp. 347-353 ◽  
Author(s):  
Michal Harel ◽  
Boris Brumshtein ◽  
Ran Meged ◽  
Hay Dvir ◽  
Raimond Ravelli ◽  
...  

3-D Structure of Serum Paraoxonase 1 Sheds Light on Its Activity, Stability, Solubility and CrystallizabilitySerum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the "good cholesterol"), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 Å resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1's active site and suggests possible mechanisms for its catalytic activity on certain substrates.


2021 ◽  
Vol 2 (03) ◽  
pp. 118-130
Author(s):  
Raghad Ali ◽  
Rayah Baban ◽  
Shatha Ali

Background: The role of paraoxonase 1 enzyme (PON1) and its single nucleotide polymorphisms (SNPs) in children with nephrotic syndrome (NS) has been reported previously in different ethnic and racial groups with divergent results. The human PON1 gene contains two coding region polymorphisms leading to two different PON1 isoforms. Objectives: The aim of the present study was to find out the association between the PON1 (Q192R and L55M) polymorphisms and their relation with serum PON1 activity as well as lipid profile tests (total cholesterol, TC; triglycerides, TG; high-density lipoprotein cholesterol, HDL-c; and low-density lipoprotein cholesterol, LDL-c) in children with NS. Methods: This study included a total of 80 participants (40 with NS in the age group of 2-14 years and 40 age and sex-matched healthy controls). The PON1 enzyme activity and lipid profile tests were measured in serum samples of all included participants. The PON1 genotype was determined by PCR-restriction enzyme fragment length polymorphism (PCR-RFLP) for both PON1 alleles (192 and 55) SNPs. Results: Our findings showed that the mean levels of lipid profile tests (TC, TG, LDL-c) were significantly increased in patients when compared with healthy controls (p<0.05), while the HDL-c concentration was significantly decreased in patients than that of controls. Also, the patients had significantly lower concentrations of PON1 when compared with the controls regardless of the genotype Q192R and L55M polymorphisms. Moreover, the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly frequent in patients when compared with the controls. Conclusions: Our results support that the presence of the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly higher in patients compared with the controls.


2015 ◽  
Vol 427 (6) ◽  
pp. 1359-1374 ◽  
Author(s):  
Moshe Ben-David ◽  
Joel L. Sussman ◽  
Christopher I. Maxwell ◽  
Klaudia Szeler ◽  
Shina C.L. Kamerlin ◽  
...  

2016 ◽  
Vol 68 (6) ◽  
pp. 1367-1376 ◽  
Author(s):  
Javier Rodríguez-Carrio ◽  
Raquel López-Mejías ◽  
Mercedes Alperi-López ◽  
Patricia López ◽  
Francisco J. Ballina-García ◽  
...  

2009 ◽  
Vol 73 (4) ◽  
pp. 760-766 ◽  
Author(s):  
Nilda Espinola-Zavaleta ◽  
María Elena Soto-López ◽  
Elizabeth Carreón-Torres ◽  
Ricardo Gamboa ◽  
Ana M. Mejía ◽  
...  

Author(s):  
Jelena Janac ◽  
Aleksandra Zeljkovic ◽  
Zorana Jelic-Ivanovic ◽  
Vesna Dimitrijevic-Sreckovic ◽  
Milica Miljkovic ◽  
...  

Background Non-alcoholic fatty liver disease is a frequent ailment with known complications, including those within the cardiovascular system. Associations between several indicators of high-density lipoprotein metabolism and function with clinical and laboratory parameters for the assessment of fatty liver index, a surrogate marker of non-alcoholic fatty liver disease, were evaluated. Methods The study comprised 130 patients classified according to fatty liver index values: fatty liver index < 30, fatty liver index 30–59 (the intermediate group) and fatty liver index ⩾ 60. Lecithin–cholesterol acyltransferase and cholesteryl ester transfer protein activities were determined. Paraoxonase 1 concentration and its activity, paraoxonase 3 concentration and high-density lipoprotein subclass distribution were assessed. Results Increased lecithin–cholesterol acyltransferase activity correlated with increased fatty liver index ( P < 0.001). Paraoxonase 3 concentration was lower in the fatty liver index ⩾ 60 group compared with the fatty liver index < 30 group ( P < 0.05). Cholesteryl ester transfer protein activity, paraoxonase 1 concentration and its activity did not significantly differ across the fatty liver index groups. The relative proportion of small-sized high-density lipoprotein 3 subclass was higher in the fatty liver index ⩾ 60 group compared with the other two fatty liver index groups ( P < 0.01). Lecithin–cholesterol acyltransferase activity positively associated with the fatty liver index ⩾ 60 group and remained significant after adjustment for other potential confounders. Only the triglyceride concentration remained significantly associated with lecithin–cholesterol acyltransferase activity when the parameters that constitute the fatty liver index equation were examined. Conclusions Higher lecithin–cholesterol acyltransferase activity is associated with elevated fatty liver index values. Significant independent association between triglycerides and lecithin–cholesterol acyltransferase activity might indicate a role of hypertriglyceridaemia in alterations of lecithin–cholesterol acyltransferase activity in individuals with elevated fatty liver index.


2003 ◽  
Vol 22 (11) ◽  
pp. 565-574 ◽  
Author(s):  
Antonio F Herńndez ◽  
Bharti Mackness ◽  
Lourdes Rodrigo ◽  
Olga López ◽  
Antonio Pla ◽  
...  

Serum paraoxonase (PON1) is a high-density lipoprotein (HDL) associated protein, which plays a critical role in the pathogenesis of atherosclerosis, although it was primarily associated with the hydrolysis of organophosphorus compounds. PON1 was initially thought to be independent from physiological or pathological states, although recently some environmental factors have been reported to modulate its activity. In this study, we have investigated the promoter (PON1-108C/T and-909 C/G) and coding region (PON1 192Q/R and 55L/M) polymorphisms, as well as PON1 activity towards different substrates (paraoxon, phenylacetate and diazoxon) in 102 individuals with long term low dose exposure to pesticides in a plastic greenhouse setting (sprayers), who are probably the group of agricultural workers with the highest exposure to pesticides. PON1 activity towards paraoxon was nonsignificantly decreased (up to 53.5%) in the sprayers subgroup exposed to organophosphates (n-41) compared with nonsprayers acting as controls (n-39). None of the genotypes studied was associated significantly with the subgroup of individuals exposed to organophosphates, although differences between sprayers and nonsprayers were observed in the PON1-909 G/C polymorphism. Among the environmental factors that significantly predicted lower rates of PON1 activity towards paraoxon are, interestingly, the exposure to organophosphates and current smoking. By contrast, the utilization of protective clothing while spraying pesticides inside the greenhouses was positively associated with PON1 activity, very likely by preventing the pesticides from being absorbed. This study suggests that chronic exposure to pesticides might decrease PON1 activity and pinpoints the potential usefulness of monitoring PON1 activity in occupational settings where exposure to organophosphates occurs.


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