Family‐based case–control study of MAOA and MAOB polymorphisms in Parkinson disease

Abstract

Monoamine oxidase (MAO) is an enzyme regulating metabolism of neurotransmitters such as dopamine. Two distinct forms of enzyme, encoded by genes MAOA and MAOB located on the X chromosome, have been considered as possible factors in the pathogenesis of Parkinson disease (PD). Previous association studies of PD and MAO genes reported inconsistent results. In this study, we used a large family-based data set to test associations between MAO genes and a risk of PD. The data set includes 298 female discordant sibpairs and 348 male discordant sibpairs. For this study, all subjects analyzed were white and families with known parkin mutations were removed. We analyzed 15 single nucleotide polymorphisms (SNPs) and a dinucleotide repeat marker in the MAO genes. Association was found with the intron 13 SNP of MAOB in the female subset (P = 0.02). No significant association was found in the male subset. Our results add to the evidence of involvement of MAOB in PD and suggest that the effect may be stronger in women.

Gene‐Gene Interaction Between FGF20 and MAOB in Parkinson Disease

“…Ascertainment and diagnosis has been described previously (van der Walt et al, 2004, Kang et al, 2006.…”

“…These families included the samples in our previous reports (van der Walt et al, 2004, Kang et al, 2006 plus about 100 newly recruited families. There were 437 singleton families and 299 multiplex families in the data set.…”

“…These SNPs cover the previously published SNPs (van der Walt et al, 2004, Kurth et al, 1993, Costa et al, 1997, Kang et al, 2006, Wu et al, 2001, a subset of HapMap SNPs, and SNPs in highly conserved genomic regions. Genomic DNA was extracted from whole blood using the PureGene system (Gentra Systems).…”

“…These symptoms manifest as a result of loss of dopaminergic neurons in the substantia nigra (SN). Indeed, two susceptibility risk genes for PD, fibroblast growth factor 20 (FGF20) (van der Walt et al, 2004, Satake et al, 2007 and monoamine oxidase B (MAOB) (Parsian et al, 2004, Mellick et al, 1999, Costa et al, 1997, Kang et al, 2006, Kurth et al, 1993 are both involved in the biological pathway regulating dopamine.…”

“…MAOB helps break down dopamine and its inhibition extends the action of dopamine in the brain. Polymorphisms in the MAOB gene were found to be associated with PD in case-control studies in whites (Costa et al, 1997, Kurth et al, 1993, an Australian cohort study (Mellick et al, 1999), subgroups (familial PD and sporadic PD with matched controls) of non-Hispanic whites (Parsian et al, 2004) and a family-based study using white families in the U.S. (Kang et al, 2006).…”