Analysis of CYP2D6 gene haplotype in patients of juvenile onset Parkinson disease

青少年起病帕金森病(YOPD)是帕金森病(PD)的亚型之一，但起病年龄在40岁以下，部分病例有遗传背景。由于其症状是同质性的，因此被认为适合于遗传背景的分析。细胞色素P450脱氢异喹羟基酶(CYP2D6)被认为是PD的主要遗传因素之一，因此，我们通过检测细胞色素P450脱氢异喹6基因的单倍型来分析YOPD与CYP2D6的关系。用Smith等人的方法检测了CYP2D6的B突变，Tuneoka等人检测了第6外显子的HHA I RFLP。据报道，在高加索人群中，B突变纯合子(debrisquine羟基酶的低代谢物)在PD中的频率相当高，但相反，我们发现它在日本人群中的频率很低，不适用于遗传标记。结论：在日本YOPD和PD样本中未发现突变纯合型，这种突变纯合型在高加索人PD中出现的频率较高。此外，YOPD组、PD组和正常对照组的HHA I RFLP等位基因频率无明显差异。这些结果表明，CYP2D6可能不是帕金森病或青光眼的危险因素。

Juvenile onset Parkinson disease (YOPD) is one of subtype of Parkinson disease (PD), but its onset age of symptom is below 40 and some cases have a genetic background. Since its symptoms are homogenous, it is considered to be suitable for analysis of genetic background. Cytochrome P450 debrisoquine hydroxylase (CYP2D6) has been regarded as one of the main genetic factor in PD.So, we analyze relationships between YOPD and CYP2D6 by determing haplotype of CYP2D6 gene polymorphisms.Genomic DNA samples are extracted from 8 YOPD, 18 PD and 55 age matched normal control. The B mutation in CYP2D6 are detected with the method by Smith et al and Hha I RFLP in exon 6 by Tuneoka et al. In Caucasian populatiopn, it is reported that the frequency of B mutation homozygous genotype (poor metabolizer of debrisoquine hydroxylase) is quite high in PD.But on the contrary, we found that its frequency is quite low in Japanese population and is not useful for genetic marker.Next, we use Hha I RFLP, which is rather high frequency in Japanese population. In conclusion, there is no mutation homozygous type, which is reported to be rather high frequency in Caucasian PD, is not found in Japanese YOPD and PD sample. Furthermore, there are no different allele frequency of Hha I RFLP between YOPD, PD and normal control. These results indicate that there is a possibility that CYP2D6 is not the risk factor of PD or YOPD.