河南汉族人口F11基因rs2036914 T/C多态性与静脉血栓栓塞症的相关性
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摘要
目的探讨河南汉族人口凝血因子XI的F11基因rs2036914 T/C多态性与静脉血栓栓塞症(VTE)的相关性。方法选择2016年3月至2017年3月在河南省人民医院住院治疗的VTE患者82例为研究对象(病例组),其中继发性VTE患者63例(继发组)。另选择性别、年龄相匹配的82例志愿者为对照组。从血液标本中提取DNA,采用PSTAR高通量位点测序技术检测对照组和病例组受试者F11基因rs2036914位点多态性。结果对照组和病例组受试者基因型分布均符合Handy-Weinberg平衡(P> 0. 05)。病例组患者等位基因C的频率高于对照组(OR=2. 192,95%可信区间:下限为1. 298、上限为3. 703,P <0. 05)。病例组患者隐性遗传模型中CC基因型频率高于对照组(OR=3. 219,95%可信区间:下限为1. 690、上限为6. 126,P <0. 01);继发组患者C等位基因频率高于对照组(OR=2. 392,95%可信区间:下限为1. 338、上限为4. 277,P <0. 05)。结论 F11基因rs2036914 T/C多态性可能是河南汉族人口发生VTE的遗传危险因素,等位基因C携带者患VTE的风险更高。
Objective To investigate the correlation between F11 gene rs2036914 T/C polymorphism and venous thromboembolism( VTE) in Han population of Henan province. Methods Eighty-two VTE patients hospitalized in Henan Provincial People's Hospital from March 2016 to March 2017 were selected as the study subjects( case group),among which63 cases were secondary VTE( secondary group). Another 82 volunteers with matching gender and age were selected as the control group. DNA was extracted from blood samples,and the polymorphism of F11 gene rs2036914 in the control group and case group was detected by PSTAR high-throughput site sequencing technology. Results The genotype distribution of both the control group and the case group was in line with Handy-Weinberg equilibrium( P > 0. 05). The frequency of allele C in the case group was higher than that in the control group( OR = 2. 192,95% CI: 1. 298-3. 703; P < 0. 05). The genotype frequency of CC of recessive genotype frequency in the case group was higher than that in the control group( OR = 3. 219,95% CI:1. 690-6. 126; P < 0. 01). The frequency of C allele in the secondary group was significantly higher than that in the control group( OR = 2. 392,95% CI: 1. 338-4. 277; P < 0. 05). Conclusion The F11 gene rs2036914 T/C polymorphism may be a genetic risk factor for VTE in the Han population of Henan province. Patients with allele C have a higher risk of VTE.
Objective To investigate the correlation between F11 gene rs2036914 T/C polymorphism and venous thromboembolism( VTE) in Han population of Henan province. Methods Eighty-two VTE patients hospitalized in Henan Provincial People's Hospital from March 2016 to March 2017 were selected as the study subjects( case group),among which63 cases were secondary VTE( secondary group). Another 82 volunteers with matching gender and age were selected as the control group. DNA was extracted from blood samples,and the polymorphism of F11 gene rs2036914 in the control group and case group was detected by PSTAR high-throughput site sequencing technology. Results The genotype distribution of both the control group and the case group was in line with Handy-Weinberg equilibrium( P > 0. 05). The frequency of allele C in the case group was higher than that in the control group( OR = 2. 192,95% CI: 1. 298-3. 703; P < 0. 05). The genotype frequency of CC of recessive genotype frequency in the case group was higher than that in the control group( OR = 3. 219,95% CI:1. 690-6. 126; P < 0. 01). The frequency of C allele in the secondary group was significantly higher than that in the control group( OR = 2. 392,95% CI: 1. 338-4. 277; P < 0. 05). Conclusion The F11 gene rs2036914 T/C polymorphism may be a genetic risk factor for VTE in the Han population of Henan province. Patients with allele C have a higher risk of VTE.
引文
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[12]李晓强,张福先,王深明.深静脉血栓形成的诊断和治疗指南(第三版)[J].中国血管外科杂志:电子版,2017,9(4):250-257.
[13]中华医学会呼吸病学分会肺栓塞与肺血管病学组.肺血栓栓塞症诊治与预防指南[J].中华医学杂志,2018,98(14):1060-1069.
[14] MARGAGLIONE M,DRANDONE E. Population genetics of venous thromboembolism. A narrative review[J]. Thromb Haemost,2011,105(2):221-231.
[15] YANNG Y,LIANG L,ZHAI Z,et al. Pulmonary embolism incidence and fatality trends in chinese hospitals from 1997 to 2008:a multicenter registration study[J]. PLoS One,2011,6(11):e26861.
[16]张建敏,马信龙,马剑雄,等.凝血因子11基因rs2289252和rs2036914多态性与静脉血栓栓塞症易感性关系的Meta分析[J].中国中西医结合急救杂志,2016,23(1):31-35.
[17] BEZEMER I D,BARE L A,DOGGEN C J,et al. Gene variants associated with deep vein thrombosis[J]. JAMA,2008,299(11):1306-1314.
[2] BRUZELIUS M,LJUNGQVIST M,BOTTAI M,et al. F11 is associated with recurrent VTE in women. A prospective cohort study[J]. Thromb Haemost,2016,115(2):406-414.
[3] MOHAMMED B M,MATAFONOV A,IVANOV I,et al. An update on factor XI structure and function[J]. Thromb Res,2018,161:94-105.
[4] BARE L A,ARELLANO A R,TONG C H,et al. Genetic variants of F11,statin use and venous thrombosis[J]. J Thromb Haemost,2011,9(6):1249-1251.
[5] WANG X,SMITH P L,HSU M Y,et al. Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice[J]. J Thromb Haemost,2006,4(9):1982-1988.
[6] TUCKER E I,MARZEC U M,WHITE T C,et al. Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI[J]. Blood,2009,113(4):936-944.
[7] MEIJERS J C,TEKELENBURG W L,BOUMA B N,et al. High levels of coagulation factor XI as a risk factor for venous thrombosis[J]. N Engl J Med,2000,342(10):696-701.
[8] GERMAIN M,CHASMAN D I,DE HAAN H,et al. Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism[J]. Am J Hum Genet,2015,96(4):532-542.
[9] LI Y,BEZEMER I D,ROWLAND C M,et al. Genetic variants associated with deep vein thrombosis:the F11 locus[J]. J Thromb Haemost,2009,7(11):1802-1808.
[10] HARRINGTON L B,WIGGINS K L,SITLANI C M,et al. The association of F11 genetic variants with the risk of incident venous thrombosis among women,by statin use[J]. Thromb Haemost,2016,115(3):682-684.
[11] DE HAAN H G,VAN HYLCKAMA VLIEG A,LOTTA L A,et al. Targeted sequencing to identify novel genetic risk factors for deep vein thrombosis:a study of 734 genes[J]. J Thromb Haemost,2018,16(12):2432-2441.
[12]李晓强,张福先,王深明.深静脉血栓形成的诊断和治疗指南(第三版)[J].中国血管外科杂志:电子版,2017,9(4):250-257.
[13]中华医学会呼吸病学分会肺栓塞与肺血管病学组.肺血栓栓塞症诊治与预防指南[J].中华医学杂志,2018,98(14):1060-1069.
[14] MARGAGLIONE M,DRANDONE E. Population genetics of venous thromboembolism. A narrative review[J]. Thromb Haemost,2011,105(2):221-231.
[15] YANNG Y,LIANG L,ZHAI Z,et al. Pulmonary embolism incidence and fatality trends in chinese hospitals from 1997 to 2008:a multicenter registration study[J]. PLoS One,2011,6(11):e26861.
[16]张建敏,马信龙,马剑雄,等.凝血因子11基因rs2289252和rs2036914多态性与静脉血栓栓塞症易感性关系的Meta分析[J].中国中西医结合急救杂志,2016,23(1):31-35.
[17] BEZEMER I D,BARE L A,DOGGEN C J,et al. Gene variants associated with deep vein thrombosis[J]. JAMA,2008,299(11):1306-1314.