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ENOS G894T Gene Polymorphisms and Hyperhomocysteinemia in the Predisposition to Venous Thromboembolism FREE TO VIEW

Zhenguo Zhai, PhD; Yanyan Li, MD; Yuanhua Yang, MD; Chen Wang, PhD
Chest. 2011;140(4_MeetingAbstracts):1065A. doi:10.1378/chest.1119893
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PURPOSE: The endothelial nitric oxide synthase (eNOS) gene may affect the expression and functional activity of the eNOS enzyme thereby reducing NO availability, which might be a logical candidate factor to be investigated for the susceptibility of venous thromboembolism (VTE).The aims of this study were to investigate the relationship of the eNOS G894T polymorphism with the risk of VTE and the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the development of VTE in a Chinese population.

METHODS: A case-control study was conducted in a general hospital. Blood samples used for DNA extraction were collected from 140 cases of VTE and 148 healthy control subjects. Single nucleotide polymorphisms (SNP) of eNOS (894G/T) were sequenced by allele specific-polymerase chain reaction (AS-PCR) analysis in all the samples. The total plasma Hcy concentrations were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The SNP (894G/T) exited in our studied subjects all met the principle of Hardy-Weinberg equilibrium. The percentage of normal homozygote, heterozygote and pathological homozygote for the eNOS G894T polymorphism in VTE patients was 81.4%,16.4% and 2.2%, respectively (controls: 90.5%,8.1% and 1.4%). Significant difference was found in the distribution of T allele in the VTE and control group (10.4% vs. 5.4%, P=0.002). Additionally, the T allele was more common in the male subjects from the VTE patients than that in the control population (11.6% vs. 5.7%, P=0.004). No association between HHcy and eNOS 894 TT genotypes was found in the VTE patients (P>0.05). The interrelation of eNOS 894 GT/TT genotype and HHcy levels did not predisposed to an increased risk of VTE [OR 0.94 (0.28-3.19)].

CONCLUSIONS: The 894G/T variant of eNOS can be considered a risk factor for VTE in the Chinese population. No association between HHcy and eNOS 894 TT genotypes was found in VTE.

CLINICAL IMPLICATIONS: The absolute biochemical rationale for the eNOS 894G>T variant to be prothrombotic is not entirely clear.In this case control study we show that eNOS 894 G/T was assocoiated with an increase in VTE in the Chinese population. Our findings could contribute to any future meta-analyses validating this polymorphism in the developemt of VTE.

DISCLOSURE: The following authors have nothing to disclose: Zhenguo Zhai, Yanyan Li, Yuanhua Yang, Chen Wang

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