Yagi Mariko, Nakamura Tsutomu, Okizuka Yo, Oyazato Yoshinobu, Kawasaki Yoko, Tsuneishi Shuichi, Sakaeda Toshiyuki, Matsuo Masafumi, Okumura Katsuhiko, Okamura Noboru
Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, Kobe, Japan.
Pediatr Int. 2010 Oct;52(5):744-8. doi: 10.1111/j.1442-200X.2010.03157.x.
In order to clarify the factors causing hyperammonemia and to predict occurrences during treatment with valproic acid (VPA), we investigated the effect of the genetic polymorphism of carbamoyl-phosphate synthase 1 (CPS14217C>A) on susceptibility of hyperammonemia, together with the effect of coadministration of other anticonvulsants.
Seventy-nine patients with epilepsy were enrolled, and five of them had hyperammonemia. Univariate and multivariate logistic regression analyses were performed.
The aspartate aminotransferase level in the patients with hyperammonemia was significantly higher than that in those without hyperammonemia. The risk of hyperammonemia was significantly influenced by the number of anticonvulsants concomitantly administered with VPA. Also, the distribution of the CPS14217C>A genotype differed depending on whether the patients had hyperammonemia or not. No significant effects of CPS14217 genotypes and the number of anticonvulsants coadministered with VPA on the serum concentrations of VPA were observed. The multivariate logistic regression analysis showed that the concomitant administration of two or more anticonvulsants with VPA and the heterozygous or homozygous carrier state of the A allele of the CPS14217C>A polymorphism were independent risk factors for developing hyperammonemia.
These findings suggested that in epileptic patients undergoing VPA therapy, CPS14217A polymorphism and the number of coadministered anticonvulsants would be considered as risk factors for hyperammonemia, even if the serum VPA concentrations were controlled.
为了阐明导致高氨血症的因素并预测丙戊酸（VPA）治疗期间的发病情况，我们研究了氨甲酰磷酸合成酶1（CPS1 4217C>A）基因多态性对高氨血症易感性的影响，以及其他抗惊厥药物联合使用的影响。
纳入79例癫痫患者，其中5例患有高氨血症。进行单因素和多因素逻辑回归分析。
高氨血症患者的天冬氨酸转氨酶水平显著高于无高氨血症患者。高氨血症的风险受与VPA联合使用的抗惊厥药物数量的显著影响。此外，CPS1 4217C>A基因型的分布因患者是否患有高氨血症而异。未观察到CPS1 4217基因型和与VPA联合使用的抗惊厥药物数量对VPA血清浓度有显著影响。多因素逻辑回归分析表明，与VPA联合使用两种或更多种抗惊厥药物以及CPS1 4217C>A多态性A等位基因的杂合或纯合携带状态是发生高氨血症的独立危险因素。
这些发现表明，在接受VPA治疗的癫痫患者中，即使血清VPA浓度得到控制，CPS1 4217A多态性和联合使用的抗惊厥药物数量也应被视为高氨血症的危险因素。
