Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease
Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease
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DOI：
10.1212/wnl.51.6.1587
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发表时间：
1998-12-01
期刊：
影响因子：
9.9
通讯作者：
Benítez, J
中科院分区：
文献类型：
--
作者：
Agúndez, JAG;Jiménez-Jiménez, FJ;Benítez, J
目的：检测121例散发性帕金森病患者和121例健康志愿者芳香胺N-乙酰转移酶(NAT2；EC 2.3.1.5)基因的7个突变的频率和连锁分布。方法：采用突变特异性聚合酶链式反应技术，从先证者的血液中提取基因组DNA。结果：帕金森病患者和对照组的NAT2基因分型比较，差异无统计学意义。然而，早发性帕金森病患者(50岁前起病，n=37)慢-乙酰化基因频率(78.4%)高于健康对照组(55.4%)和晚发性帕金森病患者(54.8%)。这种差异在统计学上是显著的(p<；0.015)，并且是慢乙酰化等位基因频率的同质性增加的结果。研究中分析的所有亚组都处于Nat2基因突变的Hardy-Weinberg平衡状态。结论：慢-乙酰化突变等位基因可能是早发性帕金森病发病机制中的低外显性基因，慢-乙酰化等位基因个体的相对风险比为2.92(95%CI，1.26-6.78)。本研究为散发性帕金森病的发病机制中遗传因素和环境因素的交互作用提供了证据。
Objective: To determine the frequency and the linkage distribution of seven mutations at the polymorphic gene coding for the arylamine N-acetyl transferase (NAT2; EC 2.3.1.5) in 121 unrelated patients with sporadic PD and in 121 unrelated healthy volunteers. Methods: The study was performed with mutation-specific PCR using genomic DNA obtained from blood of the probands. Results: Comparison of the NAT2 genotypes of the overall PD patients and control subjects did not indicate statistically significant differences. However, patients with early-onset PD (onset before the age of 50 years, n = 37) showed a higher frequency of slow-acetylation genotypes (78.4% patients) compared with both healthy control subjects (55.4%) and with late-onset (onset after 51 years of age, n = 84) PD patients (54.8%). Such a difference was statistically significant (p < 0.015) and was the result of a homogeneous increase in the frequency of slow-acetylation alleles. All subgroups analyzed in the study were in Hardy-Weinberg equilibrium for mutations at the NAT2 gene. Conclusions: Slow-acetylation-mutated alleles may be considered low-penetrance genes in early-onset PD pathogenesis, with a relative risk ratio for individuals with slow-acetylation genotype of 2.92 (95% CI, 1.26 to 6.78). This study provides evidence for the interaction of genetic and environmental factors in the etiology of sporadic PD.