Analysis of the Association Between MicroRNA Biogenesis Gene Polymorphisms and Venous Thromboembolism in Koreans

Author:

Ko Eun Ju,Kim Eo Jin,Kim Jung Oh,Sung Jung Hoon,Park Han Sung,Ryu Chang Soo,Oh Jisu,Chong So Young,Oh Doyeun,Kim Nam KeunORCID

Abstract

Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A > G, DROSHA rs10719T > C, RAN rs14035C > T and XPO5 rs11077A > C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018; XPO5 rs11077AA + AC versus CC: p < 0.001). Analysis of allele combinations of all four polymorphisms (DICER1, DROSHA, RAN, XPO5) revealed that A-T-T-A was associated with decreased VTE prevalence (p = 0.0002), and A-T-C-C was associated with increased VTE prevalence (p = 0.027). Moreover, in subjects with provoked VTE, the DROSHA rs10719T > C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p < 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects.

Funder

Korea Health Industry Development Institute

National Research Foundation of Korea

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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