Mani Balachandran, Nair Pradeep Pankajakshan, Sekhar Anamika, Kamalanathan Sadishkumar, Narayan Sunil K, Kesavan Ramasamy
Department of Neurology, JIPMER, Pondicherry, India.
Department of Neurology, JIPMER, Pondicherry, India.
Epilepsy Res. 2021 Nov;177:106786. doi: 10.1016/j.eplepsyres.2021.106786. Epub 2021 Oct 7.
To study the association between CYP2C192 (681 G > A) and UGT1A62 (552A > C) polymorphisms on Valproic acid (VPA)-induced weight gain in People with epilepsy (PWE).
We recruited PWE on VPA monotherapy and genotyped for CYP2C19 and UGT1A6 polymorphisms. Association between CYP2C19 polymorphism and weight gain was the primary outcome parameter. We followed them up monthly for six months and recorded Body mass index (BMI), drug compliance, side effects, food frequency, physical activity.
Of 108 participants recruited, we assessed the association between the polymorphism and weight gain in 101 PWE for CYP2C192 and 103 PWE for UGT1A62 polymorphism. The proportion of participants with weight gain was higher in those with poor and intermediate metabolizer genotypes of CYP2C19 (*1/*2 and *2/2) compared to extensive metabolizers (1/1) [53.3 % vs 31.7 %, RR 1.68, 95 % CI (1.01-2.79), P = 0.03]. However, CYP2C192 allele did not show an increased risk of weight gain over the CYP2C191 allele. No association could be demonstrated with UGT1A6 genotypes and weight gain. In logistic regression analysis, CYP2C192 carrier genotype was the independent predictor of weight gain. OR 2.89 [95% CI (1.07-7.84)]. There were no significant association with serum TSH, fT4, testosterone, and valproate levels with CYP2C19 or UGT1A6 polymorphisms.
People with epilepsy carrying CYP2C19 polymorphisms (*1/*2) and (*2/*2) had 3 times higher risk of VPA-induced weight gain compared to wild type (*1/*1).
研究细胞色素P450 2C192（681G＞A）和尿苷二磷酸葡萄糖醛酸基转移酶1A62（552A＞C）基因多态性与癫痫患者（PWE）丙戊酸（VPA）所致体重增加之间的关联。
我们招募接受VPA单药治疗的PWE，并对其进行细胞色素P450 2C19和尿苷二磷酸葡萄糖醛酸基转移酶1A6基因多态性基因分型。细胞色素P450 2C19基因多态性与体重增加之间的关联是主要结局参数。我们对他们进行了为期6个月的每月随访，并记录体重指数（BMI）、药物依从性、副作用、食物频率、身体活动情况。
在招募的108名参与者中，我们评估了101例PWE的细胞色素P450 2C192基因多态性和103例PWE的尿苷二磷酸葡萄糖醛酸基转移酶1A62基因多态性与体重增加之间的关联。与代谢活跃型（*1/1）相比，细胞色素P450 2C19代谢不良和中等代谢基因型（1/2和2/2）的参与者体重增加的比例更高[53.3%对31.7%，RR 1.68，95%CI（1.01-2.79），P=0.03]。然而，与细胞色素P450 2C191等位基因相比，细胞色素P450 2C192等位基因并未显示出体重增加风险增加。未发现尿苷二磷酸葡萄糖醛酸基转移酶1A6基因型与体重增加之间存在关联。在逻辑回归分析中，细胞色素P450 2C192携带基因型是体重增加的独立预测因素。OR为2.89[95%CI（1.07-7.84）]。细胞色素P450 2C19或尿苷二磷酸葡萄糖醛酸基转移酶1A6基因多态性与血清促甲状腺激素、游离甲状腺素、睾酮和丙戊酸盐水平之间无显著关联。
与野生型（*1/*1）相比，携带细胞色素P450 2C19基因多态性（*1/*2）和（*2/*2）的癫痫患者VPA所致体重增加的风险高3倍。
