Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease

The monoamine oxidase B gene (MAOB; Xp15.21-4) is a candidate gene for Park inson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of MAOB polymorphis ms (a [GT] repeat allelic variation in intron 2 and an A-G transition in in tron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1 .64) age- and gender-matched control subjects. Genomic DNA was extracted fr om venous blood and polymerase chain reaction was used to amplify the appro priate regions of the MAOB gene. The length of each (GT) repeat sequence wa s determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose g el electrophoresis. The G-A polymorphism showed no association with PD (odd s ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). T here was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi(2) = 20.09; P < 0.01). After statistical adjustment for potential confounders using a log istic regression analysis, the (GT) repeat alleles greater than or equal to 188 base pairs in the intron 2 marker of the MAOB gene were significantly associated with PD (OR = 4.60; p < 0.00005; 95% CI = 1.97-10.77). The 186 b ase pair allele was also significantly associated with PD (OR = 1.85; p = 0 .048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the MAOB gene is a powerful marker for PD in this large Australian cohort.