High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism

Syed, Salahuddin; Zargar, Mahrukh Hameed; Khan, Nabeela; Ahmad, Rehana; Shah, Zafar A.; Asimi, Ravouf

doi:10.1016/j.gene.2018.02.031

Cited by 10 publications

(5 citation statements)

References 108 publications

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“…In such a condition, inductive reasoning is not possible, and therefore the analysis of both variants was removed from the Section 3. These variants in FVL and PRT are known thrombotic factors impacting TEEs but not in SCD across various ethnic groups, including the Saudi population, as supported by previous studies [23][24][25][26][27][28][29][30]. A recent meta-analysis that included 18 studies from mixed populations comparing 30,234 VTE cases and 172,122 controls detected FVL (rs6025) as the highest signal marker (1.4 × 10 −188 ) [51].…”

Section: Discussionmentioning

confidence: 64%

“…Both variants in FVL and PRT were reported as the main contributing factors underlying recurrent pregnancy loss in Saudi females from different regions [28,29]. These two variants were also found to be more prominent in 250 TEE patients from Kashmir [30]. Furthermore, MTHFR variants (C677T (rs1801133) and A1298C (rs1801131)) were reported as risk markers in addition to FVL for developing DVT in two Iranian studies [31,32], although a previous study on a smaller number of patients failed to detect an association between DVT and MTHFR [33].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease

Alshabeeb,

Alwadaani,

Al Qahtani

et al. 2023

Genes

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Background: Sickle cell disease (SCD) is a Mendelian disease characterized by multigenic phenotypes. Previous reports indicated a higher rate of thromboembolic events (TEEs) in SCD patients. A number of candidate polymorphisms in certain genes (e.g., FVL, PRT, and MTHFR) were previously reported as risk factors for TEEs in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlie TEEs in SCD patients. Methodology: A multi-center genome-wide association study (GWAS) involving Saudi SCD adult patients with a history of TEEs (n = 65) and control patients without TEE history (n = 285) was performed. Genotyping used the 10× Affymetrix Axiom array, which includes 683,030 markers. Fisher’s exact test was used to generate p-values of TEE associations with each single-nucleotide polymorphism (SNP). The haplotype analysis software tool version 1.05, designed by the University of Göttingen, Germany, was used to identify the common inherited haplotypes. Results: No association was identified between the targeted single-nucleotide polymorphism rs1801133 in MTHFR and TEEs in SCD (p = 0.79). The allele frequency of rs6025 in FVL and rs1799963 in PRT in our cohort was extremely low (<0.01); thus, both variants were excluded from the analysis as no meaningful comparison was possible. In contrast, the GWAS analysis showed novel genome-wide associations (p < 5 × 10−8) with seven signals; five of them were located on Chr 11 (rs35390334, rs331532, rs317777, rs147062602, and rs372091), one SNP on Chr 20 (rs139341092), and another on Chr 9 (rs76076035). The other 34 SNPs located on known genes were also detected at a signal threshold of p < 5 × 10−6. Seven of the identified variants are located in olfactory receptor family 51 genes (OR51B5, OR51V1, OR51A1P, and OR51E2), and five variants were related to family 52 genes (OR52A5, OR52K1, OR52K2, and OR52T1P). The previously reported association between rs5006884-A in OR51B5 and fetal hemoglobin (HbF) levels was confirmed in our study, which showed significantly lower levels of HbF (p = 0.002) and less allele frequency (p = 0.003) in the TEE cases than in the controls. The assessment of the haplotype inheritance pattern involved the top ten significant markers with no LD (rs353988334, rs317777, rs14788626882, rs49188823, rs139349992, rs76076035, rs73395847, rs1368823, rs8888834548, and rs1455957). A haplotype analysis revealed significant associations between two haplotypes (a risk, TT-AA-del-AA-ins-CT-TT-CC-CC-AA, and a reverse protective, CC-GG-ins-GG-del-TT-CC-TT-GG-GG) and TEEs in SCD (p = 0.024, OR = 6.16, CI = 1.34–28.24, and p = 0.019, OR = 0.33, CI = 0.13–0.85, respectively). Conclusions: Seven markers showed novel genome-wide associations; two of them were exonic variants (rs317777 in OLFM5P and rs147062602 in OR51B5), and less significant associations (p < 5 × 10−6) were identified for 34 other variants in known genes with TEEs in SCD. Moreover, two 10-SNP common haplotypes were determined with contradictory effects. Further replication of these findings is needed.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease

Alshabeeb,

Alwadaani,

Al Qahtani

et al. 2023

Genes

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“…As shown, 58 in patients with deep vein thrombosis they have a higher rate of this mutation when compared with the control group (18 vs. 3.8%); others identify. For their part, 59,60 an incidence of 54% of FVL-G1691A in patients with deep vein thrombosis; a review, 61 show an increase in the rate of FVL-G1691A in patients with venous thrombosis where values of 52% are shown compared to the control group that presented values of only 14.6%, clearly expanding the knowledge of the role of FVL-G1691A in the development of venous thrombosis or deep vein thrombosis, another report. Attia F, et al, in 2009, observed the relationship between PT-G20210A and the development of deep vein thrombosis, in patients with deep vein thrombosis; a meta-analysis reports that patients with venous thrombosis have a higher incidence of PT-G20210A with values of up to 21.9% compared to the control group that presented values 62 of up to 6.1%.…”

Section: Discussionmentioning

confidence: 94%

Incidence of hereditary thrombofilies in a population of Mexican women

Manuel¹,

Estuardo²,

Jesús³

et al. 2020

OGIJ

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Objective: To report the incidence of thrombophilias and importance in the development of thrombotic events in a population of Mexican women. Methods: Is a retrospective, observational and cross-sectional study of 184 women of reproductive age, where the age, weight, height and study of hereditary thrombophilias of FVL-G1691A, PT-G20210A, MTHFR-C677T and PAI-1 4G/5G were studied. Four groups were formed: 1) FVL-G1691A, 2) PT-G20210A, 3) MTHFR-C677T and 4) PAI-1 4G/5G, each group was separated by homozygous and heterozygous mutation. Results: MTHFR-C677T and PAI-1 4G/5G present higher incidence (48.9 and 64%), when comparing with FVL-G1691A and PT-G20210A (3.8 and 0.5%) (p<0.05), higher incidence of PAI-1 4G/5G was observed, when compared to MTHFR-C677T (64.6 vs. 48.9%, p<0.05), difference that was not observed when comparing FVL-G1691A with PT-G20210A (3.8 vs. 0.5%, p>0.05). When patients presented only one thrombophilia, the highest incidence is of MTHFR-C677T and PAI-1 4G>5G (16.5 and 35.2%). Patients with multiple thrombophilias had an incidence of MTHFR-C677T with PAI-1 4G/5G of 30.2%. Conclusion: Our results in the population of Mexican women, we report a high incidence of the MTHFR-C677T and PAI-1 4G / 5G mutation, which makes them susceptible to the development of thrombotic events.

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“…As VTE is a complex disease that involves various risk factors, several SNPs, such as factor V Leiden (F5 rs6025), prothrombin 20210G > A (F2 rs1799963) and CYP4V2 (rs13146272), have been found to increase the risk of developing VTE [31, 32]. CYP4V2 , located on chromosome region 4q35 and on genes that are involved in coagulation, was reported to be associated with corneal dystrophy disease and lipid metabolism [18, 33].…”

Section: Discussionmentioning

confidence: 99%

Association of the CYP4V2 polymorphism rs13146272 with venous thromboembolism in a Chinese population

et al. 2018

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Genome-wide association studies have identified the CYP4V2 polymorphism (rs13146272) as a risk factor associated with venous thromboembolism (VTE). However, due to the small sample size and variance in genetic analysis models, the relationship between VTE and rs13146272 remains unclear. Here, we performed a case–control study to analyse the associations between rs13146272 and VTE in a Chinese population and to compare the differences among various ethnicities. In this study, 226 VTE patients and 205 healthy controls were recruited, and the allele frequency of variant rs13146272 was analysed by a MassARRAY SNP genotyping assay. In addition, 9 case–control cohorts from 5 studies involving 6667 VTE-affected individuals and 8716 control subjects were included in this meta-analysis. Pooled ORs and 95% CIs were calculated to assess the association between rs13146272 and VTE by using different genetic models. Our case–control study results showed that there was no significant association between VTE and rs13146272 under the additive model (OR = 0.92, 95% CIs: 0.70–1.21, p = 0.55) in this Chinese population. However, the results of the meta-analysis performed by merging all cohorts showed that rs13146272 was significantly associated with VTE under the additive model, recessive model and dominant model. In the additive and recessive models, the association reached the threshold for genome-wide significance ( p < 5.0e −08 ). In conclusion, our pooled systematic study results indicated that individuals with the A allele had a higher risk of developing VTE than those with the C allele of the rs13146272 variant, but the risk was inconsistent among different ethnicities. Further validation of this association with larger sample sizes and multiple ethnicities is warranted.

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High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism

Cited by 10 publications

References 108 publications

Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease

Impact of Genetic Variations on Thromboembolic Risk in Saudis with Sickle Cell Disease

Incidence of hereditary thrombofilies in a population of Mexican women

Association of the CYP4V2 polymorphism rs13146272 with venous thromboembolism in a Chinese population

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