Association of genetic variants of hemostatic system genes with venous thrombosis in children born to mothers with a burdened obstetric and gynecological history

O. A. Perevezentsev, I. S. Mamedov, D. V. Burtsev
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Abstract

Thrombophilias are hereditary and acquired conditions characterized by an excessive tendency of the body to form thrombi in the blood vessels. Idiopathic venous thrombosis can often occur in childhood and can also be associated with certain genetic variants of hereditary predisposition to thrombophilia.Purpose. To analyze the association of 8 genetic variants (F2 20210G>A, F5 1691G>A, F7 10976G>A, F13 G>T, ITGA2 807C>T, ITGB3 1565 T>C, PAI-1–675 5G>4G) with venous thrombosis in children born to mothers with a burdened obstetric and gynecological history.Material and methods. The patient group included 322 children aged 7 to 14 years (average age 9.3 years), who had a history of episodes of venous thrombosis of various locations, born to mothers with obstetric and gynecological history. The comparison group included 159 healthy children also aged from 7 to 14 years (average age 9.5 years), who did not have a history of episodes of venous thrombosis and who were also born to mothers with obstetric and gynecological history. Molecular genetic analysis was carried out using real-time PCR with automatic analysis of melting curves.Results. Based on the results of an analysis of the association of genetic variants with venous thrombosis in children born to mothers with obstetric and gynecological history, a connection with this pathology was established for genetic variants F5 1691G>A (genotype GA+AA, OR=3.33, 95% CI: 1.19 — 9.36), ITGA2 807C >T (TT genotype (OR=1.92, 95% CI:1.20 — 3.06) and heterozygous CT (OR=1.46, 95% CI: 1.10 — 1.93)) and ITGB3 1565 T>C (CC genotype (OR=2.77 95% CI:1.08 — 7.02) and TC (OR=1.40, 95% CI: 1.07 — 1.83)).Conclusion. Thus, we established an association of 3 genetic variants (Leiden mutation, ITGA2 807C>T and ITGB3 1565 T>C) with venous thrombosis in children born to mothers with obstetric and gynecological history.
有妇产科病史的母亲所生子女的止血系统基因变异与静脉血栓形成的关系
血栓性疾病是一种遗传性和获得性疾病,其特征是人体血管内过度倾向于形成血栓。特发性静脉血栓通常发生在儿童时期,也可能与血栓性疾病遗传倾向的某些基因变异有关。目的:分析8个遗传变异(F2 20210G>A、F5 1691G>A、F7 10976G>A、F13 G>T、ITGA2 807C>T、ITGB3 1565 T>C、PAI-1-675 5G>4G)与有妇产科病史的母亲所生儿童静脉血栓形成的相关性。患者组包括 322 名 7 至 14 岁的儿童(平均年龄为 9.3 岁),他们都有不同部位的静脉血栓病史,其母亲有妇产科病史。对比组包括 159 名同样年龄在 7-14 岁(平均年龄 9.5 岁)的健康儿童,他们没有静脉血栓病史,母亲也有妇产科病史。采用实时 PCR 技术进行了分子遗传分析,并对熔解曲线进行了自动分析。根据对有妇产科病史的母亲所生子女的遗传变异与静脉血栓相关性的分析结果,确定了遗传变异 F5 1691G>A(基因型 GA+AA,OR=3.33,95% CI:1.19 - 9.36)、ITGA2 807C>T(TT 基因型(OR=1.92,95% CI:1.20 - 3.06)和杂合子 CT(OR=1.46,95% CI:1.10 - 1.93))和 ITGB3 1565 T>C(CC 基因型(OR=2.77,95% CI:1.08 - 7.02)和 TC(OR=1.40,95% CI:1.07 - 1.83))。因此,我们确定了3种遗传变异(莱登突变、ITGA2 807C>T和ITGB3 1565 T>C)与有妇产科病史的母亲所生子女的静脉血栓形成有关。
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