Allele frequencies of PON1 Q192R polymorphism in four populations of India

Khurana, Priyanka; Panmei, Tabitha; Kshatriya, Gautam K.

doi:10.1016/j.etap.2015.03.001

Cited by 7 publications

(3 citation statements)

References 37 publications

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“…Furthermore, two significant variants in the PON1 gene at chromosome 7, namely rs662 (p.Q192R) and rs854560 (p.L55M), have been reported to affect clopidogrel metabolic activation in the liver by modulating the activity and stability of paraoxonase-1 enzyme. Research has shown that individuals carrying the minor R allele i.e., have glutamine Q amino acid replaced by arginine (R) in the rs662 variant (p.Q192R) tend to have higher paraoxonase-1 activity in comparison with those who have the common Q allele [ 13 ]. In contrast, the substitution of Leucine (L) amino acid with methionine (M) in the rs854560 (p.L55M) variant has been associated with a reduction in the stability of paraoxonase protein, leading to a decrease in the serum concentration of the enzyme itself [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

Khasawneh,

Alsafar,

Alblooshi

et al. 2024

Hum Genomics

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Background Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel. Methods Our study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1, and P2Y12R) in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes. Results Our data shows that approximately 37% (n = 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19 metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12 genes, potentially influencing clopidogrel’s transport, enzymatic clearance, and receptor performance. Conclusions Recognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.

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Section: Introductionmentioning

confidence: 99%

The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

Khasawneh,

Alsafar,

Alblooshi

et al. 2024

Hum Genomics

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“…PON-1 hydrolyzes paraoxon to p-nitrophenol, but it also shows a high affinity for other molecules with free amino and hydroxyl groups (Demir et al, 2019;Demir, 2020). PON-1 is a multifunctional enzyme with the capacity to act as arylesterase, lactonase, and organophosphatase (Xotlanihua-Gervacio et al, 2019;Mitra et al, 2015). PON-1 is a 43-kDa calcium-dependent glycoprotein expressed by the 9-exon PON-1 gene located on the long arm of chromosome 7 (7q21); it is synthesized in the liver and secreted into the bloodstream via association with high-density lipoproteins (HDL) (Xotlanihua-Gervacio et al, 2019;López-Flores et al, 2009;Mitra et al, 2015;Mota et al, 2019;Demir, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…PON-1 is a multifunctional enzyme with the capacity to act as arylesterase, lactonase, and organophosphatase (Xotlanihua-Gervacio et al, 2019;Mitra et al, 2015). PON-1 is a 43-kDa calcium-dependent glycoprotein expressed by the 9-exon PON-1 gene located on the long arm of chromosome 7 (7q21); it is synthesized in the liver and secreted into the bloodstream via association with high-density lipoproteins (HDL) (Xotlanihua-Gervacio et al, 2019;López-Flores et al, 2009;Mitra et al, 2015;Mota et al, 2019;Demir, 2019). The binding of PON-1 to HDL depends on terminal amino residues that anchor to phospholipids.…”

Section: Introductionmentioning

confidence: 99%

Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega, Jalisco, Mexico

CEJA-GALVEZ¹,

TORRES-S罭CHEZ²,

Torres-Jasso³

et al. 2021

Biocell

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Paraoxonase-1 (PON-1) is an enzyme that hydrolyzes organophosphate pesticides. The presence of polymorphisms in PON-1 (L55M and Q192R) decreases its enzyme activity and increases the risk of central nervous system (CNS) toxicity in occupationally exposed farmers, leading to chronic degenerative diseases and death. We studied 103 farmers in the region of Cienega Jalisco, Mexico, which were exposed mainly to organophosphate pesticides. We used serum and plasma samples to assay PON-1 activity and perform polymorphism analysis (L55M and Q192R) using qPCR and TaqMan probes, respectively. For both polymorphisms, there was high percentage of heterozygosity (55 LL = 0.19, LM = 0.75, MM = 0.06; 192 QQ = 0.12, QR = 0.72, RR = 0.16), while the allelic frequencies were more balanced (L = 0.56, M = 0.44; Q = 0.48, R = 0.52). There were no significant differences in enzyme activity of L55M polymorphism genotypes (LL = 179.27; LM = 192.11; MM = 122.11; QQ = 135.74; QR = 187.90; RR = 209; p > 0.05). But there was a slight decrease in enzyme activity for the Q192R polymorphism genotypes. The genotype and alcohol consumption associated with slight increases in enzyme activity. However, genotype and tobacco consumption did not have a significant effect on PON-1 activity (µU/mL) (p > 0.05). Overall, alcohol and tobacco consumption affected PON-1 enzyme activity (µU/mL) up to 21.1%. The data obtained in this study reveal that PON-1 activity is affected by genetic variants such as Q192R and alcohol consumption. This may influence the susceptibility of populations to organophosphate poisoning.

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Genetic variation at Q192R and L55M polymorphisms in PON1

Kshatriya

2016

Environmental Toxicology and Pharmacology

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Allele frequencies of PON1 Q192R polymorphism in four populations of India

Cited by 7 publications

References 37 publications

The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population

Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega, Jalisco, Mexico

Genetic variation at Q192R and L55M polymorphisms in PON1

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