G蛋白信号调节因子2基因C1114G多态性与儿童血管迷走性晕厥的相关性研究

Association between C1114G polymorphism in the regulator of G protein signaling 2 and vasovagal syncope in children

目的分析G蛋白信号调节因子2（RGS2）基因C1114G多态性在儿童血管迷走性晕厥（VVS）及其各临床分型组间的分布，初步探讨RGS2 C1114G与VVS的相关性。方法前瞻性病例对照研究。收集2010年8月至2015年12月在上海市儿童医院就诊的不明原因晕厥的300例患儿进行基础直立倾斜试验（HUT），选取150例HUT阳性且符合VVS诊断的患儿,设为VVS组，并根据HUT过程中心率血压变化特点，分为混合型、血管抑制型、心脏抑制型3个亚型；150例HUT阴性患儿设为HUT阴性组；另以150名健康体检儿童设为健康对照组用以检测基因多态性。比较VVS组及HUT阴性组的临床特征，同时抽取三组受试者外周血，应用高分辨率熔解曲线和聚合酶链反应结合基因测序的方法检测RGS2 C1114G多态性，并分析其基因型、等位基因频率在各组间及VVS各临床分型组间的分布。组间比较运用χ2检验。结果VVS组[男48例，女102例，年龄（10.1±3.2）岁]和HUT阴性组[男67例，女83例，年龄（10.8±2.2）岁]临床特征比较，VVS发病在性别分布上，女孩高于男孩（68.0%比57.3%），差异有统计学意义（χ2=5.090，P=0.024）；RGS2 C1114G基因型在VVS组、HUT阴性组和健康对照组的分布分别为CC：98例（65.3%）,112例（74.7%）,108名（72.0%）；CG：36例（24.0%），28例（18.7%），31名（20.7%）；GG：16例（10.7%），10例（6.7%），11名（7.3%）；等位基因频率在VVS组、HUT阴性组和健康对照组中分别为C： 232（77.3%），252（84.0%），247（82.3%）；G： 68（22.7%）, 48（16.0%）, 53（17.7%）,各基因型及等位基因频率在各组间差异均无统计学意义（χ2=3.632, P=0.458；χ2=4.659, P=0.097）。150例VVS患儿中混合型83例、血管抑制型42例、心脏抑制型25例；RGS2 C1114G基因型在以上各亚组的分布为CC：65例（78.3%），20例（47.6%），13例（52.0%）；CG：16例（19.3%），11例（26.2%），9例（36.0%）；GG：2例（2.4%），11例（26.2%），3例（12.0%）；等位基因频率在以上各亚组的分布为C：146（88.0%），51 （60.7%），35（70.0%）；G：20（12.0%），33（39.3%），15（30.0%），GG及其G等位基因在血管抑制型组中的分布高于混合型组和心脏抑制型组，且差异有统计学意义（χ2=21.698, P=0.000；χ2=25.345, P=0.000）。结论本组未发现RGS2 C1114G多态性与儿童血管迷走性晕厥发病的相关性，但GG及其G等位基因在VVS临床分型血管抑制型亚组中分布较高，推测RGS2 C1114G与VVS发作时的血压调控有相关性。

ObjectiveTo analyze the distribution of the regulator of G protein signaling 2 （RGS2） gene C1114G polymorphism in children with vasovagal syncope （VVS） and the associated clinical classification groups, and to explore the association between RGS2 C1114G and VVS.MethodsThis was a prospective case-control study. A head-up tilt test （HUT） was performed in 300 children visiting Children＇s Hospital Affiliated to Shanghai Jiaotong University from August 2010 to December 2015 for unexplained syncope. A total of 150 children with positive HUT and a diagnosis of VVS were enrolled and assigned to the VVS group. The VVS group was further divided into 3 subgroups based on characteristics of the heart rate and blood pressure measured during the HUT. A total of 150 children with negative HUT were enrolled and assigned to the HUT-negative group. A total of 150 healthy children were enrolled as the normal control group for genetic polymorphism detection. The clinical characteristics of patients in the VVS group and the HUT-negative group were recorded. Peripheral blood samples of each case were collected. RGS2 C1114G polymorphism was evaluated using high-resolution melting curve and polymerase chain reaction together with gene sequencing. The genotype and allele frequency were analyzed and compared among different groups （VVS, HUT-negative, and normal control） and VVS subgroups. Comparisons among groups were performed using Chi-square test.ResultsPatients in the VVS group （48 males and 102 females, aged （10.1±3.2） years） were more frequently female （68.0% vs. 57.3%;χ2=5.090, P=0.024） compared with patients in the HUT-negative group （67 males and 83 females, aged （10.8±2.2） years）. No significant difference was found regarding the distribution of the CC genotype, CG genotype and GG genotype among the VVS group （n=98, 65.3%; n=36, 24.0%; n=16, 10.7%）, the HUT-negative group （n=112, 74.7%; n=28, 18.7%; n=10, 6.7%） and the normal control group （n=108, 72.0%; n=31, 20.7%; n=11, 7.3%） （χ2=3.632, P=0.458）. There was no significant difference in the frequencies of C allele and G allele in the VVS group （n=232, 77.3%; n=68, 22.7%）, the HUT-negative group （n=252, 84.0%; n=48,16.0%） and the normal control group （n=247, 82.3%; n=53, 17.7%） （χ2=4.659, P=0.097）. The 150 children in the VVS group were further divided into the mixed-response subgroup （n=83）, vasodepressor-response subgroup （n=42） and cardioinhibitory-response subgroup （n=25）. The CC genotype, CG genotype and GG genotype in the mixed-response subgroup, the vasodepressor-response subgroup and the cardioinhibitory-response subgroup were （n=65, 78.3%; n=16, 19.3%; n=2, 2.4%）, （n=20, 47.6%; n=11, 26.2%; n=11, 26.2%） and （n=13, 52.0%; n=9, 36.0%; n=3, 12.0%）, respectively. The frequencies of C allele and G allele in the mixed-response subgroup, the vasodepressor-response subgroup, and the cardioinhibitory-response subgroup were （n=146, 88.0%; n=20, 12.0%）, （n=51, 60.7%; n=33, 39.3%） and （n=35, 70.0%; n=15, 30.0%）, respectively. The percentages of the GG genotype and G allele were significantly higher in the vasodepressor-response subgroup than the other two subgroups （χ2=21.698, 25.345, all P=0.000）.ConclusionsNo significant association was found between RGS2 C1114G polymorphism and VVS in children. Due to the higher distribution of GG genotype and G allele in the vasopressor-response subgroup, RGS2 C1114G may be associated with the regulation of blood pressure during the onset of VVS in children.