MTHFR A1298C Research Articles

TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine.

PP-342 Pulmonary Thromboembolism Diagnosed by Transthoracic Echocardiography in an Ulcerative Colitis Patient with Compound Heterozygous MTHFR C677T / MTHFR A1298C Mutations

Pulmonary embolism is a common problem in long term hospitalized, elderly and immobile patients and has high mortality rate if it’s not treated. Its diagnosis is sometimes very difficult. Hereditary factors, venous thromboembolism are important risk factor for these patients. Transthoracic echocardiography is a fast and noninvasive diagnostic method and used complementary to computed tomography, ventilation - perfusion scintigraphy and pulmonary angiography in the diagnosis of pulmonary thromboembolism.

MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women

The aim of this study was to investigate the association between MTHFR gene polymorphisms and IVF outcomes in Brazilian women undergoing assisted reproduction treatment. A prospective study was conducted in the Human Reproduction Department at the ABC University School of Medicine and the Ideia Fertility Institute between December 2010 and April 2012. The patient population was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms C677T and A1298C were evaluated and compared with laboratory results and pregnancy rates. The C677T variant was associated with proportions of mature (P=0.006) and immature (P=0.003) oocytes whereas the A1298C variant was associated with number of oocytes retrieved (P=0.044). The polymorphisms, whether alone or in combination, were not associated with normal fertilization, good-quality embryo or clinical pregnancy rates. This study suggests that the number and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T and A1298C.It is believed that folate has a crucial function in human reproduction and that folate deficiency can compromise the function of the metabolic pathways it is involved in, leading to an accumulation of homocysteine. The gene MTHFR encodes the 5-MTHFR enzyme, which is involved in folate metabolism, and C677T/A1298C polymorphisms of this gene are related to decreased enzyme activity and consequent changes in homocysteine concentration. Folate deficiency and hyperhomocysteinaemia can also compromise fertility and lead to pregnancy complications by affecting the development of oocytes, preparation of endometrial receptivity, implantation of the embryo and pregnancy. In folliculogenesis, hyperhomocysteinaemia can activate apoptosis, leading to follicular atresia and affecting the maturity of oocytes and the quality of embryos cultured in vitro. This study was performed to investigate the association between MTHFR polymorphisms and IVF outcomes in women undergoing assisted reproduction treatment.

Evaluation of Factor V G1691A, prothrombin G20210A, Factor XIII V34L, MTHFR A1298C, MTHFR C677T and PAI-1 4G/5G genotype frequencies of patients subjected to cardiovascular disease (CVD) panel in south-east region of Turkey

Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 -675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66%, respectively. No mutation was detected in 92 (1.95%) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.

Intraindividual Somatic Variations in MTHFR Gene Polymorphisms in Relation to Colon Cancer

MTHFR mediates the one carbon metabolism pathway. Two common genetic variants, C677T and A1298C, of MTHFR are associated with number of human diseases, including cancer, as well as being involved in the modulation of therapy outcome to antifolate drugs. To understand the distribution pattern of SNPs among different tissues of an individual, we examined MTHFR polymorphisms in normal and colon cancer tissues and compared the genotype frequencies in peripheral blood samples. DNA was isolated from tumor tissue and matched normal tissues from 155 colon cancer patients. These samples as well as DNA from blood samples of the control group (n = 294) were analyzed for MTHFR polymorphisms by PCR-RFLP and confirmed by a direct DNA sequencing method. Our data suggest that the allele and genotype frequencies of C677T and A1298C were significantly different between tumor tissues and both types of normal tissues. We have established that MTHFR variants that exist in tumor and matched normal tissues of colon cancer patients differ suggesting somatic variation in MTHFR polymorphisms among different tissues of an individual. The MTHFR A1298C polymorphism was associated with risk of colon cancer. Different MTHFR variants may exist in different tissues to maintain physiological functions and may have implications for disease susceptibility and pharmacogenomics based therapies. Original submitted 21 January 2013; Revision submitted 3 January 2014.

5,10‐Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene–environment interaction analysis in non‐syndromic cleft lip/palate

Non-syndromic cleft lip/palate (NSCL/P) is a common congenital defect in Mexico. Periconceptional intake of folic acid (FA) may reduce the risk of this malformation. Although the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme participates in folate metabolism, several studies failed to find any association between NSCL/P and the MTHFR C677T and A1298C polymorphisms. However, interactions among NSCL/P, MTHFR gene polymorphisms, and FA intake have not been explored in Mexican populations. This case-control study included 132 patients with NSCL/P and 370 controls from Mexico City. Maternal FA consumption during pregnancy was examined, as were the MTHFR C677T and A1298C polymorphisms and gene-FA interactions. Maternal FA intake during the periconceptional period was lower in cases (1.5%) than in controls (13%), with the risk of delivering a child with NSCL/P lower in mothers who consumed FA (OR=0.29, 95% CI: 0.19-0.44). In addition, the risk of NSCL/P was lower in children with the TT than the CC genotype of MTHFR C677T (OR=0.39, 95% CI: 0.23-0.68), after Bonferroni correction and exclusion of stratification. No evidence of gene-FA interaction was found. These results indicate that maternal FA intake and the TT genotype of the MTHFR C677T polymorphism in children independently reduced the risk of NSCL/P in our population.

Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility.

The aim of this study was to explore the relationship between 2 genetic polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and A1298C, and determine the long-term reproductive outcome in infertile men. This was a prospective study conducted in an andrology clinic. Men with a 1-year history of infertility were assessed for the MTHFR polymorphisms at a 5-year follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism between men who did and did not bear children during follow-up. Of the 215 men who were infertile at 1 year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception during the 5-year follow-up, with the highest rate in the first year (32.6%). The MTHFR 677TT genotype (homozygote) was associated with a substantially increased risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type). Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a risk factor for male infertility during 5-year follow-up, whereas a correlation between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility.

Association of dietary intake of folate and MTHFR genotype with breast cancer risk

We conducted a hospital-based case-control study to investigate the associations of dietary intake of folate and MTHFR C677T and A1298C polymorphisms with breast cancer in a Chinese population. A 1:1-matched case-control study was conducted. Two hundred and thirty patients who were newly diagnosed and histologically confirmed breast cancer and 230 controls were enrolled from Xinxiang Central Hospital. Folate intake was calculated by standard portion size and relative size for each food item in the questionnaire. Genotyping of MTHFR C677T and A1298C was performed by PCR-RFLP. MTHFR 677TT (OR = 2.26, 95%CI = 1.09-4.87, P = 0.02) and T allele (OR = 1.40, 95%CI = 1.03-1.90, P = 0.03) had an increased risk of laryngeal cancer when compared with the CC genotype. We found any interaction between MTHFR C677T and folate intake (P for interaction = 0.02). In conclusion, our study demonstrated that MTHFR C677T polymorphism and folate are associated with risk of breast cancer.

Association between dietary intake of folate and MTHFR and MTR genotype with risk of breast cancer.

We investigated the association between dietary intake of folate, vitamin B6, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotype with breast cancer. A matched case-control study was conducted, and 413 patients with newly diagnosed and histologically confirmed breast cancer and 436 controls were recruited. Folate intake, vitamin B6, and vitamin B12 levels were calculated, and the MTHFR C677T and A1298C and MTR A2756G polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Breast cancer cases were generally older, older at first live birth, and younger at menarche, had a higher body mass index, were smokers, had higher energy intake, and more first-degree relatives with breast cancer as well as more live births compared to controls. With respect to energy intake, we found that higher energy intake were more likely to increase the risk of breast cancer. The MTHFR 667TT genotype was associated with a moderately increased risk of breast cancer when compared with the CC genotype, and a significant odds ratio (OR; 95% confidence interval, CI) was found (OR = 1.70, 95%CI = 1.06-2.73). Individuals carrying T allele were associated with higher risk of breast cancer when compared with C allele (OR = 1.34, 95%CI = 1.06-1.70). We did not find a significant effect of the MTHFR A1298C and MTR A2756G on the risk of breast cancer. We did not find any association between folate intake and MTHFR C677T polymorphisms. In conclusion, we found that the MTHFR C667T polymorphism is associated with the risk of breast cancer, indicating that this genotype plays a role in breast cancer development.

Prevalence of MTHFR C677T and A1298C Mutations and Thrombophilia in Puerto Rico

Prevalence of MTHFR C677T and A1298C Mutations and Thrombophilia in Puerto Rico

MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: a meta-analysis of 12 genetic association studies

Chronic myelogenous leukemia (CML) is a complex disease with a genetic basis. The genetic association studies (GASs) that have investigated the association between adult CML and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have produced contradictory and inconclusive results. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the association of these polymorphisms with adult CML risk. A literature search for eligible GAS published before September 15, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using the Stata software, version 12.0. Twelve case-control studies were included in this meta-analysis with a total of 932 CML patients and 3,465 healthy controls. For MTHFR C677T (dbSNP: rs1801133, C>T), though the pooled ORs were not significant in the overall population, all the ORs greater than 1 suggested an increased risk of CML for carriers of the risk allele. However, stratified analysis based on genotyping method revealed a significant association in the PCR-restriction fragment length polymorphism (RFLP) subgroup, possibly as a result of heterogeneity. For MTHFR A1298C (dbSNP: rs1801131, A>C), the combined results showed that carriers of the C allele may be associated with a decreased risk of adult CML. Stratified analysis showed that the magnitude of this effect was especially significant among Asians, indicating ethnicity differences in adult CML susceptibility. This meta-analysis shows that the C allele of MTHFR A1298C may be associated with a decreased risk in adult CML, especially among Asians, while MTHFR C677T may not be associated with adult CML risk. However, the development of adult CML may be the result of gene-gene and gene-environment interactions, which should be considered in future individual GAS and subsequent meta-analyses.

MTHFR C677T and A1298C polymorphisms and risk of nonsyndromic orofacial clefts in a south Indian population

ObjectivesSeveral lines of evidence suggest that the decrease in folate in periconceptional period or maternal use of folate antagonists has been associated with a higher risk of orofacial clefts (OFCs). MTHFR is a critical enzyme in folate metabolism that catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, thus playing a vital role in DNA synthesis and DNA methylation. The aim of our study was to determine whether there is any association between the susceptibility to Nonsyndromic cleft lip with or without cleft palate (NSCL/P) amongst the variations of MTHFR genotypes in South Indian population. MethodsOur sample comprised 123 cases with NSCL/P and 141 controls without clefts or family history of clefting. The most common polymorphisms C677T (rs1801133) and A1298C (rs1801131) on the MTHFR gene were screened for the genotypes using PCR-RFLP. ResultsBoth C677T and A1298C are polymorphic with minor allele frequencies of 0.131 and 0.429, respectively, for controls. Genotype data in control and cleft groups are following the Hardy Weinberg Equilibrium. There were no significant differences in genotypes of both polymorphisms between controls and NSCL/P. The pairwise LD values (D′ and r2) between C677T and A1298C are 1.0 and 0.096 respectively indicating no significant LD between these two SNPs. Haplotype phenotype analysis did not show the evidence for association. Gene–gene interaction showed the distribution of the observed combinations of the two MTHFR polymorphisms was not different between NSCL/P and controls (p=0.887). ConclusionsOur results do not support the hypothesis, that variants in the MTHFR gene confer a risk for NSCL/P in the South Indian population.

Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population

Folate pathway is expected to play an important role in spermatogenesis since it is involved in DNA synthesis, repair and methylation. The purpose of this study was to examine the association between male infertility and the MTHFR (C677T and A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this study from different Jordanian infertility clinics. Of these, 150 cases of infertile men that included oligozoospermia cases (n=45), severe oligozoospermia (n=71) and azoospermia (n=34) were studied. The other 150 males were age matched fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using PCR-RFLP technique. The results showed an association between MTHFR 677TT genotype and male infertility (P<0.05). However, the distribution of MTHFR A1298C and MTRR A66G genotypes were not different between the fertile and infertile groups (P>0.05). In addition, none of the examined polymorphisms was related to any of the semen parameters in the infertile group. In conclusion, this study showed that MTHFR C677T polymorphism is associated with male infertility in Jordanians.

Serum Homocysteine and MTHFR C677T and A1298C gene polymorphisms in Type 2 Diabetic Patients with Nephropathy in Sector of Egyptian Population

Serum Homocysteine and MTHFR C677T and A1298C gene polymorphisms in Type 2 Diabetic Patients with Nephropathy in Sector of Egyptian Population

Green Tea Consumption and Breast Cancer Risk in Japanese Women: A Case-Control Study

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, only a few epidemiological studies have examined this association, and findings have been inconsistent. We examined the association between green tea consumption and breast cancer risk in consideration of the hormone receptor status of tumors and investigated whether the association was modified by dietary and genetic factors based on a hospital-based case-control study in Nagano, Japan. A total of 369 pairs completed a validated food frequency questionnaire and provided blood samples. Four single nucleotide polymorphisms (SNPs) were genotyped: CYP19A1 (rs10046), COMT (rs4680), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131). We found no inverse association between green tea consumption and breast cancer risk. Compared with women who drank less than 120 ml of green tea per day, the adjusted odds ratio for women who drank more than 600 ml was 1.27 (95% confidence interval = 0.75–2.14; P for trend = 0.20). We also found no inverse association for either tumor subtype. No substantial effect modification was observed for menopausal status, 4 SNPs, or dietary intake of folate or isoflavone. This study provides additional evidence that green tea consumption is not associated with a decreased risk.

The Effect of RFC G80A Polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms

The association between the risk of acute lymphoblastic leukemia (ALL) in children and enzymes involved in the folate metabolism has been under investigation lately. The reduced folate carrier gene (RFC) encodes reduced folate carrier, a protein that transports into the cell both folate and methotrexate, a commonly used chemotherapeutic drug, has been proved polymorphic at position 80 (G→A). The role of this polymorphism in childhood ALL and its interaction with other enzymes of the folate metabolic pathway, including MTHFR, has been examined in different populations with diverse results. In the present case-control study, 35 children with ALL and 48 healthy adult blood donors, all originating from the island of Crete (Greece), were screened for the presence of the RFC G80A polymorphism, using PCR/RFLP techniques. The effect on ALL risk and methotrexate-induced toxicities, along with the role of gene-gene interactions in our population, were examined. No significant association was observed between the RFC G80A genotypes and either the development of ALL or the presence of adverse events. However, a significant association was detected between the MTHFR A1298C/ RFC G80A genotype and a nonpredisposition for ALL (P=0.035). This study suggests that gene-gene interactions in childhood ALL may be of prognostic value in our population.

Molecular Analysis Of Patients With Deep Venous Thrombosis

Background Deep venous thrombosis (DVT) refers to the formation of a thrombus within a deep vein that frequently occurs after surgical procedures, trauma, in the presence of cancer and immobilization conditions. DVT is a major health problem that causes high rate of morbidity and mortality in the general population. Hyper coagulation states such as antithrombin-III, protein-C and protein-S deficiencies, contribute to formation of DVT. Congenital and acquired gene mutations are other risk factors that stimulate formation of thrombus. Our aims in this study was to molecularly analyze the patients with DVT and assess the impact of common mutations of MTHFR (C677T) (A1298C), PAI-1, Prothrombin 20210 and FV Leiden mutation on occurrence of deep venous thrombosis. Methods This long-term study was conducted from June 2009 to July 2013 on 221 patients with deep venues thrombosis. Two hundred and twenty-one age and sex matched individuals were also chosen as control group. The diagnosis of venous thromboembolic disease was based on patient’s history, clinical findings and D-dimer test. Finally deep venous thrombosis was confirmed with Doppler ultrasonography. In addition, all participants were asked to complete a standardized questionnaire on acquired risk factors for venous thrombosis. After confirmation of DVT, both groups were assessed molecularly for five mutations including, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, Prothrombin 20210 and FV Leiden. The relationship between these mutations and the risk of DVT was calculated using logistic regression and expressed as an OR with a 95% confidence interval (CI). Results The mean age of patients and control group were 38±0.8 and 3.7± 0.7 years. Our results revealed that the MTHFR C677T (OR 2.9, 95% 95% CI 1.1 to 7.5) and MTHFR A1298C in heterozygote manner (OR 4.3, 95% CI 1.4 to 13.7) were each associated with an increased risk of DVT. The OR associated with being a carrier of the PAI-1 4G/5G genotype was 2.9 (95% CI 1.14 to 7.5). There was a 4-fold increased risk of DVT associated with Prothrombin 20210 mutation in heterozygote manner (OR 4.3, 95% CI 1.4 to 13.7). For patients who were heterozygous for FV Leiden mutation OR DVT was 2.6 (95% CI 1.3 to 5.0). Conclusion Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT. Disclosures: No relevant conflicts of interest to declare.

Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs.The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of “unknown cause” (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C.Plasma tHcy levels were not significantly related to the IQ scores (TIQ, VIQ, or PIQ). Two significant findings came out. First, patients on AED polytherapy showed significantly lower TIQ, VIQ, and PIQ scores compared with the ones with AED monotherapy (p=0.032; p=0.008; p=0.005, respectively). However, this significant difference was not observed with the plasma tHcy levels compared with AED treatment. Second, patients with the 677TT genotype showed significantly higher tHcy levels versus those with the wt ones (p=0.049). In the latter group of patients, although the mean TIQ score was lower compared with the mean TIQ score in those with the wt ones, the difference only approached statistical significance (p=0.056). To our knowledge, this is the first study investigating the relationship between tHcy levels and cognitive scores in children with epilepsy treated with AEDs. Analysis of wider samples, selective neuropsychological tests, and prospective recruitment of patients might be encouraged.

Genotipos frecuentemente asociados a trombofilias

Venous thromboembolism is an important pathological entity that causes high morbidity due either to the disease or its complications. The incidence in the world ranges between 1:100 in adults and 1:100,000 in children. Risk factors for the disease include genetic as well as environmental factors. Among them, factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR C677T and A1298C (which until recently were considered risk factors), have been widely studied given their impact in the world. This review presents in a clear and concise way what a thrombous is and how it is formed; how a clot is able to produce thromboembolic disease; what are the main nosological entities involved, and their main genetic causes. The most epidemiologically important genetic alterations and studies conducted in Colombia will be emphasized.

Frequently associated genotypes to thrombophilia

Venous thromboembolism is an important pathological entity that causes high morbidity due either to the disease or its complications. The incidence in the world ranges between 1:100 in adults and 1:100,000 in children. Risk factors for the disease include genetic as well as environmental factors. Among them, factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR C677T and A1298C (which until recently were considered risk factors), have been widely studied given their impact in the world. This review presents in a clear and concise way what a thrombous is and how it is formed; how a clot is able to produce thromboembolic disease; what are the main nosological entities involved, and their main genetic causes. The most epidemiologically important genetic alterations and studies conducted in Colombia will be emphasized.