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17-04-2011 | Cardiology | Article

KNG1 gene polymorphism may increase venous thrombosis risk

Abstract

Free abstract

MedWire News: A polymorphism in the gene that encodes kininogen 1 (KNG1) is associated with decreased activated partial thromboplastin time (aPTT) and an increased risk for venous thrombosis (VT), study findings indicate.

Pierre-Emmanuel Morange (Université de la Méditerraneé, Marseille, France) and colleagues explain that aPTT reflects global coagulation activity, and shortened aPTT is a reliable predictor of VT.

A recent genome-wide association study identified three single nucleotide polymorphisms (SNPs) associated with aPTT levels, located in the Factor (F)XII (F12; rs27431672), histidine-rich glycoprotein (HRG; rs9898), and KNG1 (rs710446) coagulation cascade genes.

The researchers therefore hypothesized that alleles associated with shortened aPTT might also be associated with an increased risk for VT.

To test this hypothesis, they genotyped 1542 patients with VT for each of the SNPs and compared their findings with those from 1110 healthy controls.

As reported in the journal Blood, only the KNG1 rs710446 SNP was associated with VT risk. Carriers of rs710446-C allele - which converts the amino acid isoleucine into threonine at residue 581 (Ile581thr) - had a 20% increased risk for VT. Adjustment for gender, blood group, and FV Leiden did not modify this association.

To confirm these findings, the researchers tested the association in an independent sample of 596 VT patients and 590 healthy controls. In this group, carriers of the rs698078-G allele (a surrogate marker for rs710446) were 17% more likely to have VT than noncarriers.

Morange and co-authors also observed a strong correlation between plasma aPTT and rs710446, with the rs710446-C allele associated with decreased aPTT levels. However, because aPTT measurements were not available in the control group, it was not possible to test the significance of these findings.

The researchers note that they cannot exclude an association between the F12 and HRG SNPs and VT risk, but the current study was underpowered to detect their effects, if any.

The team concludes that the KNG1 Ile581Thr variant is "a new candidate risk factor for VT."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Laura Dean

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