The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: A validation study

Al‐Rasheed, Maha; Hefnawy, MennatAllah M.; Elsherif, Nourhan N.; Alhawassi, Tariq M.; Abanmy, Norah O.; AlRasheed, Nora M.; Alqahtani, Fulwah Yahya; Aleanizy, Fadilah Sfouq; Muiya, Paul; Al-Boudari, Olayan M; Dzimiri, Nduna

doi:10.1016/j.gene.2018.06.024

Cited by 5 publications

(5 citation statements)

References 34 publications

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“… 53 Other studies have confirmed that the ANRIL rs564398 variant is significantly associated with myocardial infarction after multivariate adjustments for coronary artery disease. 54 However, the present study found that the ANRIL rs564398 variant allele was not related to susceptibility to recurrent miscarriage. Because there are differences in susceptibility genes between different ethnic groups, the results of genetic susceptibility need to be verified in different populations.…”

Section: Discussioncontrasting

confidence: 79%

The lncRNA ANRIL Gene rs2151280 GG Genotype is Associated with Increased Susceptibility to Recurrent Miscarriage in a Southern Chinese Population

Che

Fang

Mai

et al. 2021

JIR

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Background Genetic factors may play an important role in susceptibility to recurrent miscarriage. Some cardiovascular disease-related candidate genes have been shown to be associated with recurrent miscarriage. Long noncoding RNA ANRIL has been confirmed to be associated with susceptibility to various diseases, such as cardiovascular disease. However, it remains unclear whether the ANRIL gene polymorphism is related to recurrent miscarriage susceptibility. Methods Three ANRIL gene polymorphisms (rs2151280, rs1063192 and rs564398) were genotyped in 819 controls and 610 recurrent miscarriage patients through TaqMan real-time polymerase chain reaction. The odds ratios and 95% confidence intervals (CIs) were used to assess the strength of each association. Results Our results showed that the ANRIL rs2151280 GG genotype was associated with increased susceptibility to recurrent miscarriage (GG vs AA: adjusted OR=1.527, 95% CI=1.051–2.218, p=0.0262; GG vs AG/AA adjusted OR=1.460, 95% CI=1.021–2.089, p=0.0381). By combining the analysis of the risk genotypes in the three SNPs, we found that individuals with 2–3 risk genotypes had a significantly increased risk of recurrent miscarriage compared with those with a 0–1 risk genotype (adjusted OR=1.728, 95% CI=1.112–2.683, p=0.0149). This risk was more significant in subgroups of women less than 35–40 years of age and women with 2–3 miscarriages. Conclusion These results suggested that a specific SNP in the ANRIL gene may be associated with increased susceptibility to recurrent miscarriage in a southern Chinese population.

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Section: Discussioncontrasting

confidence: 79%

The lncRNA ANRIL Gene rs2151280 GG Genotype is Associated with Increased Susceptibility to Recurrent Miscarriage in a Southern Chinese Population

Che

Fang

Mai

et al. 2021

JIR

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“…A study that genotyped 8 CDKN2B SNPs in 4650 Saudi Arabs to assess their association with cardiovascular risk found that the T allele of rs1333045 [0.54(0.48–0.61); p < 0.0001] was significantly associated with coronary artery disease (CAD) after adjusting for other risk factors. This finding suggests that the CDKN2B gene locus plays a critical role in cardiovascular risk among Arabs 46 . Consistently, it has been reported that the T allele at rs1333045 is statistically associated with increased susceptibility to coronary artery disease ( p < 0.0001), T2DM ( p = 0.048), and myocardial infarction ( p = 1.15E−08) 47–49 .…”

Section: Discussionsupporting

confidence: 69%

“…This finding suggests that the CDKN2B gene locus plays a critical role in cardiovascular risk among Arabs. 46 Consistently, it has been reported that the T allele at rs1333045 is statistically associated with increased susceptibility to coronary artery disease ( p < 0.0001), T2DM ( p = 0.048), and myocardial infarction ( p = 1.15E−08). 47 , 48 , 49 Noteworthy in silico analysis showed that lncRNA CDKN2B rs1333045T>C causes to gain microRNA target sites for seven microRNAs and probably has the strongest and weakest binding to hsa‐miR‐5006‐5p and hsa‐miR‐5582‐5p , respectively.…”

Section: Discussionsupporting

confidence: 52%

Genetic variations in IKZF3, LET7‐a2, and CDKN2B‐AS1: Exploring associations with metabolic syndrome susceptibility and clinical manifestations

Paniri,

Hosseini,

Fattahi

et al. 2024

Clinical Laboratory Analysis

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Background and aimMetabolic syndrome (MetS) increases the risk of atherosclerosis and diabetes, but there are no approved predictive markers. This study assessed the role of specific genetic variations in MetS susceptibility and their impact on clinical manifestations.MethodIn this study, a genotype–phenotype assessment was performed for IKZF3 (rs907091), microRNA‐let‐7a‐2 (rs1143770), and lncRNA‐CDKN2B‐AS1 (rs1333045).ResultsAnalyses indicate that while rs907091 and rs1143770 may have potential associations with MetS susceptibility and an increased risk of atherosclerosis and diabetes, there is an observed trend suggesting that the rs1333045 CC genotype may be associated with a decreased risk of MetS. The genotypes and allele frequencies of rs1333045 were significantly different between studied groups (OR = 0.56, 95% CI 0.38–0.81, p = 0.002, and OR = 0.71, 95% CI 0.55–0.92, p = 0.008), with the CC genotype displaying increased levels of HDL. Furthermore, the rs907091 TT genotype was associated with increased triglyceride, cholesterol, and HOMA index in MetS patients. Subjects with the CC genotype for rs1143770 had higher HbA1c and BMI. In silico analyses illustrated that rs907091 C remarkably influences the secondary structure and the target site of a broad spectrum of microRNAs, especially hsa‐miR‐4497. Moreover, rs1333045 creates a binding site for seven different microRNAs.ConclusionFurther studies on other populations may help confirm these SNPs as useful predictive markers in assessing the MetS risk.

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“…Numerous risk factors (smoking, unhealthy diets, obesity, physical inactivity, harmful alcohol consumption, high blood pressure, diabetes, hyperlipidemia, and genetic susceptibility) are associated with the onset, establishment, and development of CVDs. In this line, genetic polymorphisms of crucial proteins in different signal pathways have been related to CVDs (Olivi et al 2015;AlRasheed et al 2018;Haybar et al 2018;Shunmoogam et al 2018). For example, the methylenetetrahydrofolate reductase (MTHFR) enzyme (a key enzyme in the folate cycle) has been implicated as a susceptibility factor in the development of CVDs (Marosi et al 2012;Liew and Gupta 2015;Whayne 2015).…”

Section: Introductionmentioning

confidence: 99%

Occurrence of MTHFR C677T gene polymorphism and its association with atherogenic indices in Mexican women from San Luis Potosi, a preliminary study

Fernández-Macías

Ochoa-Martínez

Pérez-López

et al. 2023

Preprint

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Some genetic variants (polymorphisms) of the methylenetetrahydrofolate reductase (MTHFR) enzyme are considered a susceptibility factor in the development of cardiovascular diseases (CVDs). Therefore, this study aimed to investigate the relationship between MTHFR C677T polymorphism and levels of well-recognized atherogenic indices in a female population from San Luis Potosi, Mexico. A total of 340 women participated in the study, and MTHFR C677T genotypification was assessed using a RT-PCR assay. Also, Framingham risk score (FRS), Castelli risk index (CRI), and atherogenic index of plasma (AIP) were estimated. The allelic frequency detected was 0.43 for the MTHFR 677T-allele in the enrolled women. Besides, the mean value of AIP was significantly higher (p<0.05) for individuals with the mutant genotype (TT; 0.29 ± 0.20) contrasted to AIP values detected in people with the wild-type genotype (CC; 0.15 ± 0.20) and heterozygous genotype (CT; 0.16 ± 0.20). Similar findings were observed for CRI through MTHFR C677T genotypes (4.40 ± 1.80; 3.90 ± 1.30; and 3.60 ± 0.90; for CC, CT, and TT, respectively). No significant changes were detected for FRS values across MTHFR C677T genotypes. Lastly, significant statistical associations were identified between the TT genotype and the AIP values (odds ratio: 2.15; 95% CI: 1.95-4.95; p= 0.01). No significant associations were detected between MTHFR C677T genotypes and FRS and CRI indices values. The results found in this research agree with data that support an increased CVDs risk in MTHFR 677T-allele carriers in the human population, as AIP is considered a reliable CVDs risk biomarker.

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The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: A validation study

Cited by 5 publications

References 34 publications

The lncRNA ANRIL Gene rs2151280 GG Genotype is Associated with Increased Susceptibility to Recurrent Miscarriage in a Southern Chinese Population

The lncRNA ANRIL Gene rs2151280 GG Genotype is Associated with Increased Susceptibility to Recurrent Miscarriage in a Southern Chinese Population

Genetic variations in IKZF3, LET7‐a2, and CDKN2B‐AS1: Exploring associations with metabolic syndrome susceptibility and clinical manifestations

Occurrence of MTHFR C677T gene polymorphism and its association with atherogenic indices in Mexican women from San Luis Potosi, a preliminary study

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