High prevalence of Parkinson's disease in the Faroe Islands

Wermuth, Lene; Joensen, Poul; Bünger, Nick; Jeune, Bernard

doi:10.1212/wnl.49.2.426

Cited by 98 publications

(105 citation statements)

References 17 publications

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“…The number of PD patients is relatively higher on the Faroe Islands comparired to other countries [33], [34], [35] and the frequency of CYP2D6 poor metabolizers is twice as high as in other Caucasians. Therefore there may be an association between these two facts.…”

Section: Discussionmentioning

confidence: 87%

Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population

Halling

Petersen

Damkier

et al. 2005

Eur J Clin Pharmacol

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Objective: The purpose of the study was to study the distribution of poor and extensive metabolizers of CYP2C19 and CYP2D6 and to genotype for CYP2C8 and CYP2C9 among 312 randomly selected Faroese. Methods and Results:The participants were phenotyped for CYP2D6 with the use of sparteine. The distribution of the sparteine metabolic ratio (sparteine/didehydrosparteines) was bimodal, and 14.5% (n=44) (95% CI 10.7-18.9%) of the subjects were phenotyped as poor metabolizers. The frequency of poor metabolizers was higher (P=0.0002; χ 2 test) among the Faroese than in other European populations (7.4%). Genotype analysis for the CYP2D6*3, *4, *6 and *9 alleles were performed using real-time PCR (TaqMan®), and we found 14.6% (n=45) (95% CI 10.8-19.0%) with deficient CYP2D6 genes (*3/*4, *4/*4, *4/*6, *6/*6) in the Faroese population.The subjects were phenotyped for CYP2C19 with the use of mephenytoin and 10 subjects, i.e. 3.2% (95% CI 1.6-5.9%) were phenotyped as poor metabolizers. Genotype analysis for the CYP2C19*2 and *3 alleles was performed by PCR analysis and 2.9% (n=9) (95% CI 1.3-5.4%) of the Faroese were found to have a deficient CYP2C19 gene all explained by the CYP2C19*2/*2 genotype. The allele frequencies of the CYP2C9*2 and CYP2C9*3 alleles were 8.8% (95% CI 6.7-11.4%) and 5.3% (95% CI 3.7-7.4%), respectively, while the CYP2C8*3 allele frequency was 6.9% (95% CI 5.0-9.2%). Real-time PCR (TaqMan®) was used for both CYP2C9 and CYP2C8 genotype analyses. Conclusion:The frequency of CYP2D6 poor metabolizers is two fold higher among the Faroese population compared to other Caucasians, while the frequencies of Faroese subjects with decreased CYP2C19, CYP2C8 and CYP2C9 enzyme activity are the same as seen in other Caucasian populations. A possible consequence might be a higher incidence of side effects among Faroese patients taking pharmaceuticals that are CYP2D6 substrates.

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Section: Discussionmentioning

confidence: 87%

Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population

Halling

Petersen

Damkier

et al. 2005

Eur J Clin Pharmacol

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“…Multiple system atrophy (MSA) is a progressive neurodegenerative disease of undetermined aetiology, which affects both sexes 1 with a prevalence ranging between 2.3 and 4.9 per 100 000 in various studies, [2][3][4] and an incidence of 0.6 per 100 000 per year. 5 It usually begins in middle age, 1 hence prevalence rates among patients aged over 55 y are significantly higher (16.8-28.7 per 100 000), 4,6 and probably underestimated as patients in the general population are often misdiagnosed.…”

Section: Introductionmentioning

confidence: 99%

Erectile and urinary dysfunction may be the presenting features in patients with multiple system atrophy: a retrospective study

et al. 2003

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Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by parkinsonism and cerebellar, autonomic, urinary, and/or pyramidal dysfunction. Urinary and erectile dysfunction (ED) symptoms are prominent early features in men with MSA. Autonomic failure, considered until recently to be the cause of ED in these men, is commonly expressed through symptoms of orthostatic hypotension (OH). The aim of this retrospective study is to examine the chronological relationship between the development of urogenital symptoms and those of OH in patients diagnosed with MSA and discuss its significance in the aetiology of ED in these patients. A total of 71 male patients, referred to a Uro-Neurology department with a diagnosis of 'probable MSA', were reviewed in terms of 'autonomic' symptoms onlyFOH and lower urinary tract symptoms, accompanied by EDFpresent at the time of their referral. Laboratory investigations including anal sphincter EMG and/or autonomic function tests (AFTs) were performed in 75 and 90% of the patients, respectively. At presentation, urinary complaints were recorded in 96% of patients and ED in all patients that this was inquired about. The onset of ED had preceded the onset of bladder symptoms in 58% and the onset of OH symptoms in 91% of these men. Bladder symptoms also preceded symptoms of OH in 76% of patients. Sphincter EMG was abnormal in 91% and AFTs in 77% of the patients tested. Almost all patients with abnormal EMG had troublesome urinary symptoms. AFTs showed similar sensitivity relating to symptoms. At presentation, urogenital symptoms are common in patients with probable MSA and are often not accompanied by symptoms of OH. The earlier occurrence of ED in men with MSA suggests a lack of a causal relationship to hypotension. The notion that MSA possibly affects the dopaminergic mechanism of erectile function is discussed.

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“…Considered as a quasi-experiment, it is consistent with the high prevalence and incidence of PD among the Faroe Islanders and Greenland Inuit [10,11]. Since PD shares protein deposits with multiple system atrophy, Lewy body disease (LBD) and AD, BP infection in genetically susceptible young individuals was proposed as an environmental driver for latelife neurodegenerations.…”

mentioning

confidence: 63%