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

Abstract

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.

Keywords: Genes; Polymorphism, single nucleotide; Syncope, vasovagal.