Confirmation of the association between LRRK2 R1628P variant and susceptibility to Parkinson's disease in the Thai population

Abstract

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.