多代家系血管迷走性晕厥的遗传关联研究：涉及性别特异性 5-羟色胺信号的证据。
Genetic Association Study in Multigenerational Kindreds With Vasovagal Syncope: Evidence for Involvement of Sex-Specific Serotonin Signaling.
机构信息
Libin Cardiovascular Institute of Calgary, Alberta, Canada (R.S., M.S.R., D.R., K.M., C.M., J.J., B.G.).
Alberta Children's Hospital Research Institute, University of Calgary, Canada (J.P.).
出版信息
Circ Arrhythm Electrophysiol. 2019 Jan;12(1):e006884. doi: 10.1161/CIRCEP.118.006884.
BACKGROUND
Several studies suggest that vasovagal syncope has a genetic origin, but this is unclear. We assessed whether plausible gene variants associate with vasovagal syncope.
METHODS
We studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. The diagnosis was ascertained with the Calgary Syncope Score. Common genetic variants were genotyped for 12 genes for vascular signaling, potassium channels, the HTR1A(serotonin 5-HT1A receptor), SLC6A4(serotonin reuptake transporter), and COMT(catecholamine O-methyltransferase). Sex-specific associations between genotypes and phenotypes were tested.
RESULTS
In 9 out of 12 variants, there was no significant association between genotype and phenotype. However, the HTR1A(-1019) G alleles associated with syncope in males, but not in females ( P=0.005). CC and GG males had 9% versus 77% likelihoods of syncope. The SLC6A4 promoter L alleles associated with decreased syncope in males but increased in females ( P=0.059). The LL and SS males had 25% and 47% syncope likelihoods, whereas females had 75% and 50% syncope likelihoods. The COMT c.472 A alleles associated with decreased syncope in males but increased in females ( P=0.017). The GG and AA males had 50% and 15% syncope likelihoods, whereas females had 52% and 73% syncope likelihoods.
CONCLUSIONS
There is a sex-dependent effect of alleles of serotonin signaling and vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.
背景
几项研究表明，血管迷走性晕厥具有遗传起源，但这一点尚不清楚。我们评估了是否合理的基因变异与血管迷走性晕厥有关。
方法
我们研究了 9 个家系中的 160 名受试者，包括 82 名晕厥者和 78 名对照者。晕厥的诊断采用卡尔加里晕厥评分法确定。对 12 个血管信号、钾通道、HTR1A（5-羟色胺 5-HT1A 受体）、SLC6A4（5-羟色胺再摄取转运体）和 COMT（儿茶酚-O-甲基转移酶）基因的常见遗传变异进行基因分型。测试了基因型与表型之间的性别特异性关联。
结果
在 12 个变异中的 9 个中，基因型与表型之间没有显著关联。然而，HTR1A（-1019）G 等位基因与男性晕厥相关，但与女性无关（P=0.005）。CC 和 GG 男性晕厥的可能性分别为 9%和 77%。SLC6A4 启动子 L 等位基因与男性晕厥减少相关，但与女性晕厥增加相关（P=0.059）。LL 和 SS 男性晕厥的可能性分别为 25%和 47%，而女性晕厥的可能性分别为 75%和 50%。COMT c.472 A 等位基因与男性晕厥减少相关，但与女性晕厥增加相关（P=0.017）。GG 和 AA 男性晕厥的可能性分别为 50%和 15%，而女性晕厥的可能性分别为 52%和 73%。
结论
存在与 5-羟色胺信号和血管迷走性晕厥相关的等位基因的性别依赖性效应，支持血管迷走性晕厥生理学的 5-羟色胺假说。
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