Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity

Ibdah, Rasheed; AL-Eitan, Laith N.; Alrabadi, Nasr; Almasri, Ayah Y; Alnaamneh, Adan H; Khasawneh, Rame; Alghamdi, Mansour A.

doi:10.2147/ijgm.s287238

Cited by 8 publications

(5 citation statements)

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“…Second, the varying frequency and clinical features of hypertension in various ethnic communities may have an impact on the study’s findings [ 19 , 27 ]. Third, several techniques of sample selection, as well as inclusion and exclusion criteria, were applied [ 31 , 34 ]. Furthermore, the intricate relationships between the examined genes and other relevant genes may impact the aetiology of hypertension and the therapeutic response [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Multiple gene families have been associated with cardiovascular diseases associated with multiple genetic variants distributed among the Jordanian population. Studies have also shown that multiple SNPs could also be associated with the response to cardiovascular drugs like warfarin [ 32 – 34 ]. In this study, we aim to further investigate the possible association of selected variations ( NOS3 (rs2070744) , NOS1AP (rs10494366) , REN (rs11240688) , PLA2G4A (rs1015710) , TCF7L2 (rs4506565 , rs4132670 , and rs7917983) , ADRB1(rs1801252 and rs1801253) , and PTPRD (rs4742610 , rs10739150 , and rs12346562) with hypertension in the Jordanian population and the effect on drug response and clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

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PTPRD gene variant rs10739150: A potential game-changer in hypertension diagnosis

AL-Eitan

2024

PLoS ONE

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Background High blood pressure, also known as hypertension (HTN), is a complicated disorder that is controlled by a complex network of physiological processes. Untreated hypertension is associated with increased death incidence, rise the need for understanding the genetic basis affecting hypertension susceptibility and development. The current study sought to identify the genetic association between twelve single nucleotide polymorphisms (SNPs) within seven candidate genes (NOS3, NOS1AP, REN, PLA2G4A, TCF7L, ADRB1, and PTPRD) Methods The current study included 200 Jordanian individuals diagnosed with hypertension, compared to 224 healthy controls. Whole blood samples were drawn from each individual for DNA isolation and genotyping. The SNPStats tool was used to assess haplotype, genotype, and allele frequencies by the mean of chi-square (χ2). Results Except for rs10739150 of PTPRD (P = 0.0003), the genotypic and allelic distribution of the SNP was identical between patients and controls. The prevalence of the G/G genotype in healthy controls (45.5%) was lower than in hypertension patients (64.3%), suggesting that it might be a risk factor for the disease. PTPRD TTC genetic haplotypes were strongly linked with hypertension (P = 0.003, OR = 4.03). Conclusion This study provides a comprehensive understanding of the involvement of rs10739150 within the PTPRD gene in hypertension. This new knowledge could potentially transform the way we approach hypertension diagnosis, providing an accurate diagnostic tool for classifying individuals who are at a higher risk of developing this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PTPRD gene variant rs10739150: A potential game-changer in hypertension diagnosis

AL-Eitan

2024

PLoS ONE

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“…More than 30 genes were found to associate with warfarin efficiency [15]. Numerous studies have investigated the correlation between various gene families polymorphisms and variability in warfarin dose and time required to arrive at the therapeutic INR in Jordanians and other ethnicities [13,14,17,34,36,43,44]. However, there is no report stating the correlation between MEF2A and SLC22A3-LPAL2-LPA polymorphisms in Jordanian cardiovascular disease patients and warfarin responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Effect of MEF2A and SLC22A3-LPAL2-LPA gene polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients

AL-Eitan,

Almasri,

Alnaamneh

et al. 2023

PLoS ONE

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Aims This study aims to investigate the influence of MEF2A and SLC22A3-LPAL2-LPA polymorphisms on cardiovascular disease susceptibility and responsiveness to warfarin medication in Jordanian patients, during the initiation and maintenance phases of treatment. Backgrounds Several candidate genes have been reported to be involved in warfarin metabolism and studying such genes may help in finding an accurate way to determine the needed warfarin dose to lower the risk of adverse drug effects, resulting in more safe anticoagulant therapy. Methods The study population included 212 cardiovascular patients and 213 healthy controls. Genotyping of MEF2A and SLC22A3-LPAL2-LPA polymorphisms was conducted to examine their effects on warfarin efficiency and cardiovascular disease susceptibility using PCR-based methods. Results One SNP (SLC22A3-LPAL2-LPA rs10455872) has been associated with cardiovascular disease in the Jordanian population, whereas the other SNPs in the MEF2A gene and SLC22A3-LPAL2-LPA gene cluster did not have any significant differences between cardiovascular patients and healthy individuals. Moreover, SLC22A3-LPAL2-LPA rs10455872 was correlated with moderate warfarin sensitivity, the other SNPs examined in the current study have not shown any significant associations with warfarin sensitivity and responsiveness. Conclusion Our data refer to a lack of correlation between the MEF2A polymorphism and the efficacy of warfarin treatment in both phases of treatment, the initiation, and maintenance phases. However, only rs10455872 SNP was associated with sensitivity to warfarin during the initiation phase. Furthermore, rs3125050 has been found to be associated with the international normalized number treatment outcomes in the maintenance phase.

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“…The pathophysiological path of its influence on pathological processes and disease is still unknown, but the role of rs4977574 polymorphism in the development of cardiovascular diseases (CVD) has been proven by many studies around the world. Ibdah et al in their study established the association of this polymorphism with CVD in the Jordanian population [23]. A large metaanalysis found a link between the polymorphism of rs4977574 A/G ANRIL gene in the Asian and Caucasian ethnic groups [24].…”

Section: Modelmentioning

confidence: 97%

Analysis of the Association of Rs4977574-Polymorphic Variants of the Anril Gene With the Development of Acute Coronary Syndrome in Individuals With Different Body Mass Index in the Ukrainian Population

Kniazkova¹,

Harbuzova

2022

EUMJ

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The objective was to analyze the association of rs4977574-polymorphic variants of the ANRIL gene with the development of acute coronary syndrome in individuals with different body mass index. Materials and methods. The venous blood of 429 people (234 patients with acute coronary syndrome and 195 people in the control group) was used for the study. Genotyping of patients by rs4977574-polymorphic variants of the ANRIL gene was performed by real-time polymerase chain reaction (Real-time PCR) in the presence of TaqMan assay C_31720978_30. Statistical analysis of the results of the study was performed using SPSS software (version 17.0). Results. The distribution of genotypes according to SNP rs4977574 of the ANRIL gene in the group of patients with ACS and the control group among individuals with BMI < 25 kg/m2 does not differ. Among patients with BMI 25 kg/m2 the genotype distribution of the rs4977574-polymorphic variant of the ANRIL gene was statistically significant (р = 0.035). In the group of patients with BMI > 25 kg/m2 according to recessive (Pobserv = 0.014; ORobserv = 1.876, 95 % СІ = 1.137–3.095) and additive (Рobserv = 0.014; ORobserv = 2.118, 95% СІ = 1.166–3.849) models of inheritance before making adjustment, people with G/G genotype had a double risk of acquiring ACS than carriers of the dominant allele. After the adjustment, corresponding models of inheritance had the same risk rate – for recessive model (Рadjust = 0.013; ORadjust = 1.951, 95% СІ = 1.149–3.313) and additive model (Рadjust = 0.026; ORadjust = 2.039, 95 % СІ = 1.087–3.826). Conclusions. Individuals with BMI > 25 kg/m2, which were carriers of G/G genotype had a 2 times higher risk to acquire ACS than the individuals with the dominant allele. Prospects for further research. Further research will be aimed at studying the impact of ANRIL polymorphism upon the risk of ACS development depending on other risk factors.

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Impact of PCSK9, WDR12, CDKN2A, and CXCL12 Polymorphisms in Jordanian Cardiovascular Patients on Warfarin Responsiveness and Sensitivity

Cited by 8 publications

References 40 publications

PTPRD gene variant rs10739150: A potential game-changer in hypertension diagnosis

PTPRD gene variant rs10739150: A potential game-changer in hypertension diagnosis

Effect of MEF2A and SLC22A3-LPAL2-LPA gene polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients

Analysis of the Association of Rs4977574-Polymorphic Variants of the Anril Gene With the Development of Acute Coronary Syndrome in Individuals With Different Body Mass Index in the Ukrainian Population

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