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Objective: To 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. Methods: This 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. Results: Patients in the VVS group (48 males and 102 females, aged (10.1±3.2) years) were more frequently female (68.0% vs . 57.3%;χ(2)=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%) (χ(2)=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%) (χ(2)=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 (χ(2)=21.698, 25.345, all P= 0.000). Conclusions: No 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.

Objective: Investigate the association between GNB3C825T gene polymorphism and pediatric vasovagal syncope., Method: Syncope group consisted of 54 cases of unexplained syncope in children, including 18 males and 36 females, at the age of 11.8 years; control group consisted of 54 healthy children over the same period, of whom 20 were male and 34 female, at the age of 11.2 years. The patients underwent head-up tilt test (HUTT). According to HUTT test results, HUTT-positive group and HUTT-negative group were further classified. For cases in HUTT-positive group, based on the changes in blood pressure and in heart rate during HUTT, vasodepressor, mixed and cardioinhibitory patterns were studied. DNA was extracted from peripheral blood in all the patients. A pair of primers was designed flanking 825 polymorphic loci. Products were recovered by using polymerase chain reaction (PCR). GNB3C825T polymorphism was detected by using gene-side GNB3C825T sequencing. Allele distribution between the various groups were studied., Result: Among fifty-four children with syncope, HUTT was positive in 30 cases, including vasodepressor pattern in 15 cases (50.0%), mixed pattern in 9 cases (30.0%) and cardioinhibitory pattern in 6 cases (20.0%). Whereas the subjects in control group had negative HUTT response. GNB3C825T allele C in the control and syncope groups was 81.5% and 65.7%, respectively. GNB3C825T allele T in the control and syncope groups was 18.5% and 34.3%, respectively (χ(2) = 6.888, P < 0.05). GNB3C825T allele C in HUTT-positive and negative groups was 61.7% and 81.3%, respectively. And GNB3C825T allele T in HUTT-positive and negative groups was 38.3% and 18.7%, respectively (χ(2) = 4.905, P < 0.05). GNB3C825T allele frequency did not show statistically significant difference among the 3 hemodynamic patterns of VVS (χ(2) = 0.658, P > 0.05)., Conclusion: Study on GNB3C825T allele frequency in children with vasovagal syncope is of significant value for a better understanding of the pathophysiology of VVS and provide a molecular biologic basis for its mechanisms.