Soga Yoshihiko, Nishimura Fusanori, Ohtsuka Yoko, Araki Hiroaki, Iwamoto Yoshihiro, Naruishi Hisa, Shiomi Nobuyuki, Kobayashi Yoshitomo, Takashiba Shogo, Shimizu Kenji, Gomita Yutaka, Oka Eiji
Department of Patho-physiology/Periodontal Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Life Sci. 2004 Jan 2;74(7):827-34. doi: 10.1016/j.lfs.2003.07.018.
Previous studies suggested that the onset of phenytoin-induced gingival overgrowth depended on serum phenytoin concentration. Cytochrome P450 2C (CYP2C) plays an important role in phenytoin metabolism. Recently, single nucleotide polymorphisms in the coding region of CYP 2C influencing phenytoin metabolism were identified. The purpose of the present study was to see if CYP 2C polymorphisms might relate to the onset and severity of phenytoin-induced gingival overgrowth. Twenty-eight epileptic patients taking phenytoin aged 15 to 75 (mean age: 42.2 years old, 20 males and 8 females) and 56 unrelated healthy subjects aged 30 to 48 (mean age: 36.8 years old, 48 males and 8 females) were examined for CYP 2C polymorphisms. All epileptic subjects were examined for the degree of gingival overgrowth, daily phenytoin dose and serum phenytoin concentration. The results indicated about 7% of the subjects including epileptic and healthy subjects examined were positive for CYP 2C93. However, the degree of gingival overgrowth did not directly correlate with CYP 2C polymorphisms. Nevertheless, the subjects with severer gingival overgrowth exhibited significantly higher serum phenytoin concentration, indicating that phenytoin metabolism is an important determinant for the severity of the disease. Additionally, CYP 2C93 carriers exhibited significantly higher serum drug concentration to drug dose. Therefore, we concluded although the gene analysis is not directly related to diagnose the disease itself, it can be utilized in estimating serum phenytoin concentration from drug dose, which in turn serves to predict the future development and clinical course of the disease.
先前的研究表明，苯妥英钠所致牙龈增生的发病取决于血清苯妥英钠浓度。细胞色素P450 2C（CYP2C）在苯妥英钠代谢中起重要作用。最近，已鉴定出CYP 2C编码区影响苯妥英钠代谢的单核苷酸多态性。本研究的目的是观察CYP 2C多态性是否可能与苯妥英钠所致牙龈增生的发病及严重程度相关。对28例年龄在15至75岁（平均年龄：42.2岁，男20例，女8例）服用苯妥英钠的癫痫患者和56例年龄在30至48岁（平均年龄：36.8岁，男48例，女8例）无亲缘关系的健康受试者进行CYP 2C多态性检测。对所有癫痫受试者检查牙龈增生程度、每日苯妥英钠剂量和血清苯妥英钠浓度。结果显示，包括癫痫患者和健康受试者在内的约7%的受检者CYP 2C93呈阳性。然而，牙龈增生程度与CYP 2C多态性无直接相关性。尽管如此，牙龈增生较严重的受试者血清苯妥英钠浓度显著更高，表明苯妥英钠代谢是该疾病严重程度的一个重要决定因素。此外，CYP 2C93携带者血清药物浓度与药物剂量之比显著更高。因此，我们得出结论，尽管基因分析与疾病本身的诊断无直接关系，但它可用于根据药物剂量估算血清苯妥英钠浓度，进而有助于预测疾病的未来发展和临床病程。
