Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway.
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
J Thromb Haemost. 2018 Jan;16(1):83-89. doi: 10.1111/jth.13892. Epub 2017 Nov 27.
Essentials Body height and prothrombotic genotypes are associated with risk of venous thromboembolism (VTE). The joint effect of prothrombotic genotypes and tall stature on VTE risk is scarcely investigated. We investigated the joint effect of prothrombotic genotypes and tall stature on VTE risk. Prothrombotic genotypes did not yield excess risk of VTE in subjects with a tall stature.
Background Studies have reported synergistic effects of prothrombotic single-nucleotide polymorphisms (SNPs) and obesity on the risk of venous thromboembolism (VTE). Tall stature is associated with an increased VTE risk, but the joint effect of prothrombotic genotypes and tall stature on the VTE risk is unknown. Aims To investigate the joint effects of prothrombotic genotypes and tall stature on the VTE risk. Methods Cases with incident VTE (n = 676) and a randomly selected age-weighted subcohort (n = 1842) were sampled from the Tromsø study (cohort follow-up: 1994-2012). DNA was genotyped for rs6025 (factor V Leiden), rs1799963 (FII), rs8176719 (ABO blood group), rs2066865 (fibrinogen-γ), and rs2036914 (FIX). Age-adjusted and sex-adjusted hazard ratios (HRs) of VTE were calculated by categories of risk alleles (de Haan 5-SNP score: 0-1, 2-3, and ≥ 4) and body height (< 40th, 40th-80th and > 80th percentiles). Results The VTE risk increased by increasing category of body height, and subjects with height ≥ 178 cm had a two-fold higher VTE risk (HR 2.03; 95% confidence interval [CI] 1.51-2.73) than those with height ≤ 165 cm. The VTE risk also increased across categories of risk alleles. However, the combination of a tall stature and risk alleles, either individual SNPs or risk score, did not result in an excess VTE risk. Subjects with four or more risk alleles and height ≥ 178 cm had a two-fold (HR 2.08; 95% CI 1.24-3.52) higher VTE risk than subjects ≤ 165 cm with no risk allele or one risk allele. Conclusions In contrast to obesity, the presence of prothrombotic genotypes did not result in an excess VTE risk in subjects with a tall stature.
研究易栓症基因型和身材高大对静脉血栓栓塞症（VTE）风险的联合作用。
从特罗姆瑟研究（队列随访：1994-2012 年）中抽取了 676 例新发 VTE 病例和 1842 名年龄加权亚组随机选择的个体。对 rs6025（因子 V Leiden）、rs1799963（FII）、rs8176719（ABO 血型）、rs2066865（纤维蛋白原-γ）和 rs2036914（FIX）进行基因分型。通过风险等位基因（de Haan 5-SNP 评分：0-1、2-3 和≥4）和身高（<40 百分位、40-80 百分位和>80 百分位）类别计算 VTE 的年龄调整和性别调整危险比（HR）。
VTE 风险随身高类别的增加而增加，身高≥178cm 的患者 VTE 风险增加两倍（HR 2.03；95%置信区间 [CI] 1.51-2.73），而身高≤165cm 的患者 VTE 风险增加两倍（HR 2.03；95%置信区间 [CI] 1.51-2.73）。风险等位基因类别也增加了 VTE 风险。然而，高身材和风险等位基因（无论是单个 SNP 还是风险评分）的组合并没有导致 VTE 风险增加。与身高≤165cm、无风险等位基因或一个风险等位基因的患者相比，有四个或更多风险等位基因且身高≥178cm 的患者 VTE 风险增加两倍（HR 2.08；95%CI 1.24-3.52）。
与肥胖不同，在身材高大的患者中，存在易栓症基因型并不会导致 VTE 风险增加。
