Pulkes Teeratorn, Papsing Chutima, Thakkinstian Ammarin, Pongpakdee Sunsanee, Kulkantrakorn Kongkiat, Hanchaiphiboolkul Suchat, Tiamkao Somsak, Boonkongchuen Pairoj
Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Parkinsonism Relat Disord. 2014 Sep;20(9):1018-21. doi: 10.1016/j.parkreldis.2014.06.013. Epub 2014 Jun 21.
LRRK2 p.R1628P (c.4883G > C) is associated with Parkinson's disease (PD) in Chinese and Thais. However, some studies in other East Asian ethnic groups did not observe this association. Carriers of p.R1628P are about 3-5% Chinese and Thais. In contrast, Japanese, Koreans and Malays are much less prevalent (0-<1%). The contradictory results may be caused by insufficient sample sizes especially studies in ethnic groups with low prevalence, which, theoretically need a much larger sample size. We conducted a case-control Thai PD study with appropriate size in order to support the role of p.R1628P related to susceptibility to PD.
Estimated total sample size of 958 Thai subjects was needed. 485 PD patients and 480 controls were recruited. The p.R1628P was screened by RFLP and confirmed by direct sequencing. Clinical characteristics were compared between PD patients with and without p.R1628P.
54 PD patients (11%) and 29 control subjects (6%) carried p.R1628P. Multiple logistic regression analysis showed that GC and CC genotypes were significantly higher in PD patients than in controls (OR = 1.81, 95%CI = 1.10-2.97). The PD patients carrying p.R1628P had earlier age at onset (56 ± 13 vs 60 ± 12; P = 0.021) and a more rapidly progressive course (P < 0.001) than the patients carrying wild-type nucleotide.
We confirm the association between p.R1628P and risk of developing PD in the appropriated sample-sized cohort. Certain LRRK2 variants appear to be generally distributed among East Asians, however, in widely different frequencies. In order to study role of such variants in PD, it should be carefully estimated the appropriate sample size.
LRRK2基因p.R1628P（c.4883G＞C）在中国人群和泰国人群中与帕金森病（PD）相关。然而，其他东亚种族的一些研究未观察到这种关联。p.R1628P的携带者在中国人群和泰国人群中约占3% - 5%。相比之下，日本、韩国和马来西亚人群中的患病率则低得多（0% - ＜1%）。这些相互矛盾的结果可能是由于样本量不足，特别是在患病率较低的种族中的研究，理论上需要更大的样本量。我们进行了一项样本量合适的泰国PD病例对照研究，以支持p.R1628P与PD易感性相关的作用。
估计总共需要958名泰国受试者作为样本。招募了485例PD患者和480名对照。通过限制性片段长度多态性（RFLP）筛选p.R1628P，并通过直接测序进行确认。比较携带和不携带p.R1628P的PD患者的临床特征。
54例PD患者（11%）和29名对照受试者（6%）携带p.R1628P。多因素logistic回归分析显示，PD患者中GC和CC基因型显著高于对照组（比值比[OR] = 1.81，95%置信区间[CI] = 1.10 - 2.97）。携带p.R1628P的PD患者发病年龄更早（56±13岁对60±12岁；P = 0.021），病程进展比携带野生型核苷酸的患者更快（P＜0.001）。
我们在样本量合适的队列中证实了p.R1628P与发生PD风险之间的关联。某些LRRK2变体似乎在东亚人群中普遍存在，然而，频率差异很大。为了研究此类变体在PD中的作用，应仔细估计合适的样本量。
