Genetic causes of Parkinson’s disease in the Maltese: a study of selected mutations in LRRK2, MTHFR, QDPR and SPR

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-016-0327-x) contains supplementary material, which is available to authorized users.