Association of vWA and TPOX Polymorphisms with Venous Thrombosis in Mexican Mestizos

Abstract

Objective. Venous thromboembolism (VTE) is a multifactorial disorder and, worldwide, the most important cause of morbidity and mortality. Genetic factors play a critical role in its aetiology. Microsatellites are the most important source of human genetic variation having more phenotypic effect than many single nucleotide polymorphisms. Hence, we evaluate a possible relationship between VTE and the genetic variants in von Willebrand factor, human alpha fibrinogen, and human thyroid peroxidase microsatellites to identify possible diagnostic markers. Methods. Genotypes were obtained from 177 patients with VTE and 531 nonrelated individuals using validated genotyping methods. The allelic frequencies were compared; Bayesian methods were used to correct population stratification to avoid spurious associations. Results. The vWA-18, TPOX-9, and TPOX-12 alleles were significantly associated with VTE. Moreover, subjects bearing the combination vWA-18/TPOX-12 loci exhibited doubled risk for VTE (95% CI = 1.02–3.64), whereas the combination vWA-18/TPOX-9 showed an OR = 10 (95% CI = 4.93–21.49). Conclusions. The vWA and TPOX microsatellites are good candidate biomarkers in venous thromboembolism diseases and could help to elucidate their origins. Additionally, these polymorphisms could become useful markers for genetic studies of VTE in the Mexican population; however, further studies should be done owing that this data only show preliminary evidence.

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

“…All these clinical manifestations contribute substantially to atherothrombosis development. In the light of this evidence, TH alterations have been associated with diverse CVDs [22,[73][74][75].…”

“…Of these, ALOX5, IL6, LPA and MMP9 gene polymorphisms were involved in inflammatory processes [9,24,[40][41][42][43]. Another three gene polymorphisms (eNOS, HMOX1 and NOX4) were involved in oxidative stress processes, and the vWA and TPO gene polymorphisms were involved in the coagulation mechanisms [13][14][15][16]22,44]. The detailed information about these nine polymorphisms is depicted in electronic supplementary material, table S3.…”

“…Polymorphisms in genes encoding to thyroid hormones and the von Willebrand factor have been related to platelet aggregation, thrombus formation and hypofibrinolysis, and, in turn, the risk of ischaemic stroke and coronary heart disease [21]. Previously, our research group reported the contributions of two tetranucleotide polymorphisms with venous thromboembolism: (i) in thyroid peroxidase gene (TPO), and (ii) in the von Willebrand factor (vWA) gene, suggesting a possible contribution to atherothrombosis [22].…”

Forensic Autosomal Short Tandem Repeats and Their Potential Association With Phenotype

“…vWF is a glycoprotein that plays a role in platelet adhesion during coagulation; therefore, it is understood that alterations in serum levels of vWF can contribute to thrombosis disorders (Laird et al, 2007). Meraz-Rios et al (2014) found that vWA-18, TPOX-9, and TPOX-12 were observed more frequently in individuals with venous thrombosis in the Mexican mestizo population. Furthermore, vWA and TPOX have been associated with chronic myeloid leukemia (Wang et al, 2012).…”

“…The markers nominated for CODIS were specifically chosen due to their location within non-coding regions of the genome; however, claims that non-coding regions play no functional role have been contested in recent years (Cole, 2007;Kaye, 2007;Sarkar and Adshead, 2010). There is increasing evidence that there may be associations between certain STR alleles and medical conditions (von Wurmb-Schwark et al, 2011;Meraz-Rios et al, 2014). This should not be confused with situations where alleles or loci are diagnostic for medical conditions (e.g., trisomy).…”