title: Association of mutations in the glucocerebrosidase gene with Parkinson disease in a Korean population.
abstract: Recent studies have shown an association between Parkinson disease (PD) and mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA), which is deficient in patients with Gaucher disease. In Asian populations, 2 mutational analysis studies have been performed in all exons of GBA; one study in a Japanese population showed the highest odds ratio among all ethnic groups, whereas the other study in ethnic Chinese observed a trend of a higher frequency of GBA mutation in PD patients without statistical significance. To investigate whether there is an association between PD and mutations of GBA in a Korean population, we analyzed mutations of GBA and compared mutation frequencies between Korean PD patients and a control population. We analyzed mutations in GBA by sequencing exons of GBA in 277 Korean PD patients and 291 control subjects. All exons of GBA were sequenced in all PD cases and 100 control subjects. Exon 2 and exons 5-11, where mutations of GBA were found in our PD patients, were analyzed in an additional 191 control subjects. Five different pathogenic heterozygous GBA mutations, including N188S, P201H, R257Q, S271G, and L444P, were identified in 9 PD cases (3.2%), whereas there were no GBA mutations found in control subjects (p<0.01, OR 20.6, 95% CI 1.2-356.4). The mean age-at-onset of heterozygous GBA variants carriers was younger than that of non-carriers (48.6±11.9 versus 57.9±13.5, p<0.05, Mann-Whitney test). Our results suggest that heterozygous mutations of GBA represent a risk factor for PD in Koreans.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Republic of Korea.
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Choi
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Kim
authors.forename: Chul Hyoung
authors.initials: CH
authors.lastname: Lyoo
authors.forename: Suk Yun
authors.initials: SY
authors.lastname: Kang
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.forename: Jong Sam
authors.initials: JS
authors.lastname: Baik
authors.forename: Seong-Beom
authors.initials: SB
authors.lastname: Koh
authors.forename: Hyeo-Il
authors.initials: HI
authors.lastname: Ma
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Sohn
authors.forename: Myung Sik
authors.initials: MS
authors.lastname: Lee
authors.forename: Yun Joong
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D056910:Republic of Korea; D012307:Risk Factors
chemical_list: D005962:Glucosylceramidase