Genetic causes of Parkinson's disease in the Maltese: a study of selected mutations in LRRK2, MTHFR, QDPR and SPR.
Mutations in Leucine-rich repeat kinase 2 NM_198578 (LRRK2 c.6055G > A (p.G2019S), LRRK2 c.4321C > G (p.R1441G)) and alpha-synuclein NM_000345 (SNCA c.209G > A (p.A53T)) genes causing Parkinson's disease (PD) are common in Mediterranean populations. Variants in the Quinoid Dihydropteridine Reductase NM_000320 (QDPR c.68G > A (p.G23D)), Sepiapterin Reductase NM_003124 (SPR c.596-2A > G) and Methylenetetrahydrofolate Reductase NM_005957 (MTHFR c.677C > T and c.1298A > C) genes are frequent in Malta and potential candidates for PD.



178 cases and 402 control samples from Malta collected as part of the Geoparkinson project were genotyped for MTHFR polymorphisms, QDPR and SPR mutations. Only PD and parkinsonism cases were tested for SNCA and LRRK2 mutations.



LRRK2 c.4321C > G and SNCA c.209G > A were not detected. The LRRK2 c.6055G > A mutation was found in 3.1 % of Maltese PD cases. The QDPR mutation was found in both cases and controls and did not increase risk for PD. The SPR mutation was found in controls only. The odds ratios for MTHFR polymorphisms were not elevated.



The LRRK2 c.6055G > A is a cause of PD in the Maltese, whilst QDPR c.68G > A, SPR c.596-2A > G and MTHFR c.677C > T and c.1298A > C are not important determinants of PD.
Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta.
Charmaine
C
Zahra
Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta.
Christine
C
Tabone
Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta.
Graziella
G
Camilleri
Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta.
Alex E
AE
Felice
Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta.
Rosienne
R
Farrugia
Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta. stephanie.bezzina-wettinger@um.edu.mt.|Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta. stephanie.bezzina-wettinger@um.edu.mt.
Stephanie
S
Bezzina Wettinger
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D004093:Dihydropteridine Reductase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008319:Malta; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D004093:Dihydropteridine Reductase; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Alpha-synuclein; Leucine-rich repeat kinase 2; Maltese; Methylenetetrahydrofolate Reductase; Parkinson’s Disease; Quinoid Dihydropteridine Reductase; Sepiapterin Reductase