CPSI T1405N polymorphism, HDL cholesterol, homocysteine and renal function are risk factors of VPA induced hyperammonemia among epilepsy patients

被引：6

作者：

Chen, Lanlan ^{[1
,5
]}

Tian, Qiuxiang ^{[1
,4
]}

Zhang, Miaoran ^{[3
]}

Chen, Deyu ^{[3
]}

Ga, Xue ^{[3
]}

Yang, Hongqun ^{[5
]}

Li, Haitao ^{[5
]}

Li, Chengnan ^{[5
]}

Wen, Jianping ^{[3
]}

Li, Yulin ^{[1
,4
]}

Tian, Xin ^{[2
]}

Chen, Peng ^{[1
,3
,4
]}

机构：

[1] Jilin Univ, Coll Basic Med Sci, Key Lab Pathobiol, Minist Educ, Changchun 130021, Jilin, Peoples R China

[2] Jilin Univ, Hosp 2, Dept Pediat, Changchun 130021, Jilin, Peoples R China

[3] Jilin Univ, Dept Genet, Coll Basic Med Sci, Changchun 130021, Jilin, Peoples R China

[4] Jilin Univ, Dept Pathol, Coll Basic Med Sci, Changchun 130021, Jilin, Peoples R China

[5] Jilin Univ, Clin Med Sch, Changchun 130021, Jilin, Peoples R China

来源：

EPILEPSY RESEARCH | 2019年 / 154卷

关键词：

CPS1; polymorphism; Valproic acid; Hyperammonemia; Epilepsy; Heart disease; Renal function; GENOME-WIDE ASSOCIATION; SYNTHETASE; DEFICIENCY; VALPROIC-ACID; HEART-DISEASE; METABOLISM; HYPERHOMOCYSTEINEMIA; PHENOTYPE; GENOTYPE; STROKE; GENE;

D O I：

10.1016/j.eplepsyres.2019.05.010

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Purpose: Valproic acid (VPA) is frequently used in the treatment of epilepsy. The adverse effects of VPA include hyperammonemia (HA) which is characterized by abnormally elevated blood ammonia level. Carbamoyl-Phosphate Synthase 1 (CPS1) is an enzyme catalyzing the initial step of removing ammonia from blood. Studies have demonstrated that the CPS1 polymorphism rs1047891-A allele carriers were susceptible to VPA-induced HA. However, the evidences remained controversial. In this study, we sought to validate the association between rs1047891 and VPA-induced HA by combining the association results from previous studies together. Methods: We first conducted a systematic meta-analysis to determine whether rs1047891 was statistically significant. Then, we further evaluated the pleiotropic effects of rs1047891 using published genome-wide association studies (GWAS) and UKBB results. A conditional analysis was conducted to investigate whether the association between rs1047891 and VPA-induced HA was mediated by cardiovascular or renal disease risk factors or vice versa. Results: The allelic, dominant and recessive ORS of rs1047891-A were all significant in our fixed-effect meta-analysis. In GWAS catalog and UKBB data, rs1047891 was associated with basal metabolic rate, adiposity and hematology traits, cardiovascular and renal disease risk factors. We further proved that plasma HDL cholesterol and homocysteine level, in addition to eGFR by serum creatinine, were associated with VPA-induced HA risk independently from rs1047891 polymorphism. Conclusion: In conclusion, the SNP rs1047891 was associated with VPA-induce HA among epilepsy patients. Meanwhile, plasma HDL cholesterol and homocysteine level had independent effects from it.

引用

页码：139 / 143

页数：5