Hyperhomocysteinemia and the compound heterozygous state for methylene tetrahydrofolate reductase are independent risk factors for deep vein thrombosis among South Indians

Abstract

To investigate the role of methylene tetrahydrofolate reductase (MTHFR) (677 C-->T and 1298 A-->C), factor V (1691 G-->A), factor II (20210 G-->A) genetic polymorphisms and hyperhomocysteinemia in the aetiology of deep vein thrombosis (DVT) in 163 cases and 163 controls. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping, reverse-phase high-performance liquid chromatography for plasma homocysteine, and Student's t-test and Fisher exact tests were used for statistical analysis. Elevated mean plasma homocysteine levels were observed in DVT cases irrespective of gender differences. Homocysteine elevation above the 95th percentile of the control group associated with 9.4-fold and 7.6-fold increased risk for DVT in men and women, respectively. Genotyping showed the MTHFR 677CT/1298AC genotype (i.e. compound heterozygosity) is associated with 3.5-fold risk for thrombosis. The factor V Leiden mutation frequency was higher in DVT cases, but not statistically significant; however, genetic predisposition to this mutation was associated with early age of DVT onset. Factor II mutation was absent in cases and controls. Co-segregation of two or more risk factors was associated with 11.7-fold increased risk for thrombosis. This study projects that hyperhomocysteinemia and compound heterozygous state for MTHFR are independent risk factors for DVT among South Indians.

Homocystine Levels, Polymorphisms and the Risk of Ischemic Stroke in Young Asian Indians

“…[25][26][27] That homocysteine levels are higher in a stroke population is a definite fact confirmed by the results from this study, which seems to be in agreement with most studies from across the world 28-30 as well as from India. 31 We also find in our study that the OR rises as we move from the first quartile to the fourth quartile of the homocysteine levels (Fig 2).…”

Frequency of Thrombophilic Gene Mutations in Patients with Deep Vein Thrombosis and in Women with Recurrent Pregnancy Loss

“…Heterozygous MTHFR C677T genotype among Saudi female patients with DVT was 6 (10%) and did not reach the significance level (P = 0.558), in agreement with a previous report stating that there is no association between MTHFR C677T and DVT [18]. Several studies revealed that the association between MTHFR C677T and the increased risk of VTE is still controversial [19]. Others suggest that the risk of this mutation is weak, increasing in older patients and with co-inheritance …”

Influence of Acquired and Genetic Risk Factors on the Prevention, Management, and Treatment of Thromboembolic Disease

“…These mutations may or may not lead to hyperhomocysteinemia, depending on the homozygosity or heterozygosity of the mutation, coinheritance with another mutation, or the presence of concurrent B vitamin deficiency [39]. The association between MTHFR C 677 T and MTHFR A 1298 C genetic polymorphism and the increased risk for VTE is still controversial [40, 41]. Ray et al suggest that the risk of these mutations is weak and is increasing in older patients and with coinheritance with other mutations [42].…”