The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

Neuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
Neurogenetics (Impact Factor: 2.88). 09/2008; 9(4):271-6. DOI: 10.1007/s10048-008-0140-6
Source: PubMed


The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] approximately 4%) and Gly2385Arg variants (PAR approximately 6%) yields a total PAR of approximately 10%.

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Available from: Yah-Huei Wu-Chou
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    • "Korea 923 PD, 422 controls 119 YOPD 814 LOPD Combined OR 1.83 (í µí±ƒ = 0.017) YOPD OR 2.28 (í µí±ƒ = 0.098) LOPD OR 1.81 (í µí±ƒ = 0.022) Ross et al., 2011 [19] Asian Taiwanese 369 PD, 300 controls Korean 844 PD, 587 controls Japanese 173 PD, 95 controls Combined 1,386 PD, 982 controls OR 1.62 * í µí±ƒ value not stated OR 1.87 * í µí±ƒ value not stated OR 1.44 * í µí±ƒ value not stated OR 1.73 (í µí±ƒ = 0.0026) Current study Malaysia 695 PD, 507 controls OR 2.22 (í µí±ƒ = 0.019) R1628P (c.4883G>C), rs33949390 Mata et al., 2005 [15] Europe, Asia, and North America 100 PD probands with family history of parkinsonism, 300 controls MAF 0.01 Lu et al., 2008 [18] "
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    ABSTRACT: The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.
    Full-text · Article · Aug 2014 · BioMed Research International
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    • "On the contrary, Gly2385Arg was rare or even absent in Malay, Indian, Norwegian or Caucasian populations [23] [32] [33]. The second recently hotspot variant in LRRK2 gene was Arg1628Pro, presenting in PD patients at higher frequency compared to controls in ethnic Chinese population in Taiwan, Singapore and some parts of mainland China [17] [24] [29] [36] [38], while this variant was hardly seen in Japan, Caucasian, Malay and Indian populations [24] [30]. Pro755Leu (c.2264c>t, rs34410987) was reported to be a mutation responsible for PD in mainland China in 2006 [35], but the studies investigated in Taiwan and Singapore [7] [26] showed that it was present with similar frequency in cases and controls, and was regarded as an irrelevant variant for increasing PD risk, which makes its role as a susceptible variant for PD in Chinese population still ambiguous to date. "
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    ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disease resulting from complex interaction involving genetic and environmental risk factors on background of aging. In terms of genetic risk factors, recent studies provided a growing number of evidence for the idea that certain polymorphisms in familiar Parkinsonism genes may contribute to risk for sporadic PD in populations of specific ethnic backgrounds. To address this issue, a case-control study was conducted to determine the prevalence of LRRK2 Pro755Leu variant in 401 patients with sporadic PD and 398 unrelated healthy controls in Han population from mainland China. Heterozygous LRRK2 Pro755Leu variant was found in four patients and two healthy controls, but no statistical differences in genotypic or allelic frequencies between PD and control groups (genotype: P=0.686; allele: P=0.687) were detected. Furthermore, to evaluate its role in ethnic Chinese population, a meta-analysis was performed on Pro755Leu in population of Chinese ancestry throughout Asia. And it was detected at a similar frequency in PD and control cohort (Z=0.48, P=0.63, odds ratio=1.44, 95% CI: 0.32-6.40). Given these findings, it was quite reasonable to suppose that LRRK2 Pro755Leu variant rarely increased risk for PD in ethnic Chinese population in Asia.
    Full-text · Article · Mar 2011 · Neuroscience Letters
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    • ", has also been identified with higher risk for PD among Han Chinese by two additional independent groups. Taken together, this supports evidences that p.Arg1628Pro variant is a second risk factor for PD in this population [Lu et al., 2008; Tan et al., 2008c]. "
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    ABSTRACT: Mutation in the LRRK2 gene is a known genetic cause of Parkinson disease (PD). However, due to the high frequency in which the most frequent LRRK2 mutation is present and the large size of LRRK2 gene, a complete sequence-based screening of the entire coding region has only been performed by a few researchers. In addition, normal variability in the LRRK2 gene has only been fully assessed in the North American population. Although a complete examination of the entire gene is required to assess the exact contribution of LRRK2 to the etiology of PD, more than 50 variants have been reported to date within the LRRK2 locus. Gene multiplications or deletions have not been reported so far. Here, all LRRK2 variants reported are interpreted and their contribution to the disease is examined.
    Full-text · Article · May 2009 · Human Mutation
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