We have investigated the urinary recovery of S-oxide metabolites of the probe aliphatic sulfide (thioether) compound S-carboxymethyl-L-cysteine (SCMC) in Parkinson's (PD), motor neurone (MND) and Alzheimer's (AD) diseases since previous studies in small populations have indicated a defect in S-oxide formation. In this study, 201 controls, 175 PD, 86 MND and 23 AD patients were investigated for their ability to produce urinary S-oxide metabolites of SCMC. The patient populations showed significantly higher number of individuals in the none S-oxide forming phenotype (39.4% PD, 38.3% MND, 56.5% AD compared to 6.9% of the control population). This results in odds risk ratios of 10.5 (PD), 10.04 (MND) and 15.21 (AD) for an individual developing these three diseases if they are unable to produce S-oxide metabolites of SCMC. The ability to form S-oxide metabolites from aliphatic sulfide compounds may be a protection mechanism against environmental/dietary sulfur containing toxins or protoxins. Med Sci Res 27:119-120 (C) 1999 Lippincott Williams & Wilkins.

OBJECTIVETo determine whether reported genetic association of polymorphisms in the CYP2D6, CYP1A1, N-acetyltransferase 2 (NAT2), DAT1, and glutathione s-transferase M1 (GSTM1) genes with PD were evident in a population of 176 unrelated patients with sporadic PD and to extend these findings to other disease groups (familial PD [n = 30], ALS [n = 50], multiple system atrophy [n = 38], progressive supranuclear palsy [n = 35], and AD [n = 23]).METHODSA combination of allele-specific PCR and analysis of restriction fragment length polymorphisms were performed.RESULTSWe genotyped 1,131 individuals. After matching each patient with a control subject by age, sex, ethnicity, and geographic origin, there was no association of any allele/genotype with any of the six disease groups. There was an increased frequency of NAT2 slow acetylators in the ALS group compared with controls (70% versus 50%; OR 2.33 [95% CI, 1.03 to 5.30]), but this was not significant after adjusting for multiple testing.CONCLUSIONSThis is one of the most extensive candidate gene studies performed in PD and the first time that some of these loci have been studied in multiple system atrophy and progressive supranuclear palsy. In contrast with previous studies, we found no role for these polymorphisms in the etiology of PD, ALS, multiple system atrophy, progressive supranuclear palsy, or AD.

The association of the Cyp 2D6 genotype in Parkinson's disease (PD) has been actively investigated in recent years. The results to date indicate an association with the Cyp 2D6*4A allele, implying that there will be an overrepresentation of the heterozygous dominant genotype in a PD population. This should then result in an over representation of the intermediate metaboliser (IM) phenotype in PD patients. We have studied the incidence of the IM and poor metaboliser (PM) phenotype in PD, motor neurone and Alzheimer's disease patients from the UK. The results show that neither the IM nor the PM phenotype were significantly different from those in the control population (P > 0.05, chi(2) test with Yate's correction) and indicate that decreased Cyp 2D6 activity was not a risk factor for these three diseases. Med Sci Res 27:281-283 (C) 1999 Lippincott Williams & Wilkins.

Objective: To confirm whether a dinucleotide repeat sequence in an intron of the microtubule-associated protein tau is associated with progressive supranuclear palsy (PSP) in an independent study population and to establish an improved methodology for allelotyping. Background: It has recently been reported that a genetic variant of tau, known as the A0 allele, was represented excessively in PSP patients when compared with control subjects. Methods: In a multicenter study, the authors examined the allelic distribution of this dinucleotide repeat marker in a set of clinically ascertained PSP patients (n = 30), multiple system atrophy (MSA) patients (n = 35), and matched control subjects (n = 70). Individuals were allelotyped using automated analysis of fluorescently labeled PCR products. Results: The A0 allele was significantly overrepresented in the PSP patients (93.3% versus 76.4%; p = 0.0067; odds ratio [OR] = 4.33; 95% confidence interval [CI], 1.36 to 13.60), but not in the MSA patients. Likewise, A0 homozygotes were overrepresented in the PSP group (86.7% versus 61.1%; p = 0.02; OR = 4.14; 95% CI, 1.19 to 14.48) compared with control subjects. Conclusions: The findings of this study, which is the largest to date, support those of a previous investigation that used pathologically confirmed PSP patients. These data provide additional strong evidence that genetic variation at or near the tau gene plays an important role in the pathogenesis of PSP.