Prevalence of prediabetes and type 2 diabetes in two non-random populations aged 44-77 years in the Faroe Islands.

AIMS: The prevalence of type 2 diabetes is increasing worldwide but little known about the status in the Faroe Islands. The aim was therefore to determine the prevalence of type 2 diabetes mellitus and prediabetes in two non-random populations aged 44-77 years. METHODS: This cross-sectional survey was conducted between 2011 and 2012 and included two sub-populations, namely 518 Septuagenarians aged 74-77 years (84% of the invited) and 401 Mark aged 44-73 years (87% of the invited). Subjects were screened for glycosylated haemoglobin, type A1c, non-fasting random plasma glucose, fasting plasma glucose followed by an oral glucose tolerance test. The screening was based on a diagnostic algorithm that included screening, diagnostic and confirmatory steps. RESULTS: Each group was analysed separately. In the Septuagenarian group 20.4% had type 2 diabetes, with 5.2% being newly detected and a total of 59% had prediabetes. In the Mark group 4.1% had diabetes, with 2.1% being newly detected and 22.3% had prediabetes. Diabetes increased with age and was significantly more prevalent among men. Women had lower mean fasting plasma glucose concentrations and men had lower values for 2-hours plasma glucose. Significant predictors associated with diabetes mellitus included obesity (BMI ≥ 30, abnormal waist/hip ratio and vegetable consumption. CONCLUSIONS: Among the Faroese populations studied, the prevalence of type 2 diabetes increased with age and was more prevalent among men. The detected prevalence was comparable to other Nordic countries for all age-groups.

Both rare and common genetic variants contribute to autism in the Faroe Islands.

The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.

Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS).

Semen quality may be adversely affected by exposure to environmental chemicals such as polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances (PFASs) that are persistent and may act as endocrine disrupting compounds. The aim of this study was to explore whether PCBs or PFASs exposure were associated with abnormalities in semen quality or reproductive hormones in Faroese men. This population based cross-sectional study includes 263 Faroese men (24⁻26 years) who delivered a semen sample for assessment of sperm concentration, total sperm count, semen volume, morphology and motility. A blood sample was drawn and analyzed for reproductive hormones, PCBs and PFASs. Exposure to ∑PCBs and perfluorooctane sulfonate (PFOS) was positively associated with sex hormone-binding globulin (SHBG) and luteinizing hormone (LH). In addition, total testosterone (T) was positively associated with ∑PCB. Both PCBs and PFOS appear to lead to increased SHBG, perhaps mediated via the liver. The higher total T associated with PCB may represent a compensatory adaption to elevated SHBG levels to maintain an unchanged free testosterone concentration. The positive association to LH for both PCBs and PFOS may indicate a direct adverse effect on the testosterone producing Leydig cells.

Carnitine levels and mutations in the SLC22A5 gene in Faroes patients with Parkinson's disease.

INTRODUCTION: Mitochondrial dysfunction, oxidative stress and energy production have been implicated in the etiology of Parkinson's disease (PD). Several agents are under investigation for potential neuroprotective effects including acetyl-l-carnitine (ALC). OBJECTIVE: To investigate whether low carnitine levels and mutations in the SLC22A5 gene encoding the carnitine transporter are associates with PD risk in the Faroe Islands where the prevalence of both PD and carnitine transporter deficiency (CTD) is high. METHODS: We conducted a case-control study with 121 cases and 235 randomly selected controls, matched by gender and age. Blood spots were analyzed for free and total carnitine levels by QUATTRO LC triple quadrupole mass spectrometry (MS/MS) and sequencing performed for five genetic mutations in the SLC22A5 gene with ABI PRISM 3130. RESULTS: PD cases had significantly lower levels of free and total carnitine levels compared with controls (P < .001). However, stratifying according to mutation status, the lower levels of carnitine was only evident among the non-mutation carriers. Specifically, no difference was found in c.95A > G mutation frequency in the SLC22A5 gene among cases and controls (p = .70). CONCLUSION: Low carnitine levels seem to be associated with PD, but only in individuals without the c.95A > G mutation rendering the carnitine transporter less efficient. Thus, the difference in carnitine levels is not caused by a higher frequency of c.95A > G mutation carriers in cases. The cause may be dietary or due to different gut microbiota among cases.

Prevalence of type 2 diabetes and prediabetes in the Faroe Islands.

AIMS: To determine the prevalence of type 2 diabetes mellitus and prediabetes among the population aged 40-74 years in the Faroe Islands. METHODS: This population-based cross-sectional survey, conducted between 2011 and 2012, invited 2186 randomly selected individuals (corresponding to 11.1% of the entire population aged 40-74 years). Subjects were screened using finger capillary blood for glycosylated hemoglobin, type A1c, non-fasting random plasma glucose, fasting plasma glucose followed by oral glucose tolerance test. The test was based on an algorithm that accounts for screening, diagnostic and confirmatory steps. Anthropometric measures and a questionnaire including medical history, medication, hereditary conditions, and food intake were included. RESULTS: The study included 1772 participants. Of the 1772, 169 (9.5%) had type 2 diabetes mellitus (3.0% of which were diagnosed upon study inclusion), thus 31.4% of subjects with diabetes were undiagnosed at the time of examination. A total of 271 (15.3%) had prediabetes. Diabetes was more prevalent among men, significantly from age ≥60 years. Women had lower mean fasting plasma glucose concentrations and men had lower values for 2-h plasma glucose. Predictors associated with diabetes mellitus included obesity (BMI ≥ 30), abnormal waist/hip ratio, history of hypertension or cardiovascular attack and family history of diabetes mellitus and leisure activity. CONCLUSIONS: The prevalences of diabetes and prediabetes increased with age and were more frequent among men. The detected prevalence in the Faroe Islands was slightly higher than other Nordic countries.

Overview of ongoing cohort and dietary studies in the Arctic.

This article gives an overview of the ongoing cohort and dietary studies underlying the assessment of population health in the Arctic. The emphasis here is on a description of the material, methods and results or preliminary results for each study. Detailed exposure information is available in an article in this journal, whereas another paper describes the effects associated with contaminant exposure in the Arctic. The cohort descriptions have been arranged geographically, beginning in Norway and moving east to Finland, Sweden, Russia and the other Arctic countries and ultimately to the Faroe Islands. No cohort studies have been reported for Alaska or Iceland.

Health effects associated with measured levels of contaminants in the Arctic.

The Human Health Assessment Group has over the past decade recommended that effect studies be conducted in the circumpolar area. Such studies examine the association between contaminant exposure in the Arctic populations and health effects. Because foetuses and young children are the most vulnerable, effect studies are often prospective child cohort studies. The emphasis in this article is on a description of the effects associated with contaminant exposure in the Arctic. The main topics addressed are neurobehavioural, immunological, reproductive, cardiovascular, endocrine and carcinogenic effect. For each topic, the association between exposure and effects is described, and some results are reported for similar studies outside the Arctic.

Sperm Aneuploidy in Faroese Men with Lifetime Exposure to Dichlorodiphenyldichloroethylene (p,p´-DDE) and Polychlorinated Biphenyl (PCB) Pollutants.

BACKGROUND: Although it is known that sperm aneuploidy contributes to early pregnancy losses and congenital abnormalities, the causes are unknown and environmental contaminants are suspected. OBJECTIVES: Our goal was to evaluate associations between lifetime exposure to organochlorines, specifically dichlorodiphenyldicholorethylene (p,p´-DDE) and polychlorinated biphenyls (PCBs), and sperm aneuploidy in men from the general population of the Faroe Islands, a population with a known history of organochlorine exposures. METHODS: Serum and semen samples from men (n = 90) 22-44 years old who participated in Faroe Islands health studies were analyzed for p,p´-DDE and PCBs 118, 138, 153, and 180 and adjusted for total lipids. Cord blood and age-14 serum were available for a subgroup (n = 40) and were also analyzed for p,p´-DDE and PCBs. Sperm fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine rates of XX18, XY18, YY18, and total disomy. Multivariable adjusted Poisson models were used to estimate the relationship between organochlorine exposure and sperm disomy outcomes. RESULTS: Adult p,p´-DDE and total PCB serum concentrations were both associated with significantly increased rates of XX18, XY18, and total disomy. Age-14 p,p´-DDE and PCB concentrations were both associated with significantly increased rates of XX, XY, and total disomy in adulthood. Associations between cord blood concentrations of p,p´-DDE and PCBs and sperm disomy in adulthood were not consistently significant. CONCLUSIONS: Organochlorine exposures measured at age 14 and in adulthood were associated with sperm disomy in this sample of high-exposure men, suggesting that the impacts of persistent pollutants on testicular maturation and function require further investigation. CITATION: Perry MJ, Young HA, Grandjean P, Halling J, Petersen MS, Martenies SE, Karimi P, Weihe P. 2016. Sperm aneuploidy in Faroese men with lifetime exposure to dichlorodiphenyldichloroethylene (p,p´-DDE) and polychlorinated biphenyl (PCB) pollutants. Environ Health Perspect 124:951-956; http://dx.doi.org/10.1289/ehp.1509779.

Vitamin d in the general population of young adults with autism in the faroe islands.

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15-24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism.

The role of vitamin D levels and vitamin D receptor polymorphism on Parkinson's disease in the Faroe Islands.

The role of vitamin D in Parkinson's disease (PD) has been proposed and both low serum 25-hydroxyvitamin D levels (25(OH)D) and vitamin D receptor polymorphisms (VDR) have been linked to PD. The aim of this study is to investigate the associations among 25(OH)D and three VDR polymorphisms and PD in the Faroese population where the prevalence of PD is high. We conducted a case-control study where 121 cases were studied for 25(OH)D levels and VDR polymorphisms against 235 randomly selected controls, matched by gender and age. No significant difference was observed in 25(OH)D levels between PD cases and controls (P=0.49), although cases had slightly lower values than controls. As well, no differences were found in genotype frequencies between cases and controls in the VDR polymorphisms studied (ApaI, BsmI, TaqI) (P=0.70, P=0.56 and P=0.54, respectively). However, we found that VDR ApaI/AC genotype was significantly associated with 25(OH)D levels (P=0.01). Although our results indicate no association between PD and vitamin D polymorphisms and/or 25(OH)D levels, the study cannot exclude a weak association. However, the known doubling in PD prevalence in the Faroe Islands cannot be explained by the polymorphisms examined in the VDR gene or the 25(OH)D levels and has to be explored further.

Semen quality and reproductive hormones in Faroese men: a cross-sectional population-based study of 481 men.

OBJECTIVES: To determine semen quality and reproductive hormone levels in young Faroese men. DESIGN: Descriptive cross-sectional study of Faroese men compared with Danish men. SETTING: Faroese one-centre study. PARTICIPANTS: 481 men born from 1981 to 1987 and investigated from 2007 to 2010. OUTCOME MEASURES: Sperm concentration, semen volume, total sperm count, sperm motility, sperm morphology and reproductive hormone levels. RESULTS: Sperm concentrations for the Faroese men were lower than for the Danish men (crude median 40 vs 48 mill/ml, p<0.0005). Semen volume was higher, and thus the total sperm counts did not differ (159 vs 151 mill, p=0.2). Motility and morphology did not differ between the Faroese and Danes. The inhibin B/follicle-stimulating hormone ratios for the Faroese men were lower than for the Danes (64 vs 76, p=0.001). Similarly, lower total testosterone/luteinising hormone (LH) ratio (4.6 vs 6.0, p<0.0005) and lower calculated free-testosterone/LH ratio (94 vs 134, p<0.0005) were detected for the Faroese men. CONCLUSIONS: Semen quality among the Faroese men is at the same low level as reported for Danish men, and the reproductive hormone levels furthermore indicated a lower Leydig cell capacity for testosterone production. The influence of environmental exposure and genetic factors on semen quality has to be studied further.

Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations.

PURPOSE: To determine the distribution of clinically important CYP2C genotypes and allele frequencies in healthy Nordic populations with special focus on linkage disequilibrium. METHODS: A total of 896 healthy subjects from three Nordic populations (Danish, Faroese, and Norwegian) were genotyped for five frequent and clinically important CYP2C allelic variants: the defective CYP2C8*3, CYP2C9*2, CYP2C9*3, and CYP2C19*2 alleles, and the CYP2C19*17 allele that causes rapid drug metabolism. Linkage disequilibrium was evaluated and CYP2C haplotypes were inferred in the entire population. RESULTS: Ten CYP2C haplotypes were inferred, the most frequent of which (49%) was the CYP2C wildtype haplotype carrying CYP2C8*1, CYP2C9*1, and CYP2C19*1. The second most frequent haplotype (19%) is composed of CYP2C19*17, CYP2C8*1, and CYP2C9*1. This predicted haplotype accounts for 99.7% of the CYP2C19*17 alleles found in the 896 subjects. CONCLUSION: CYP2C19*17 is a frequent genetic variant in Nordic populations that exists in strong linkage disequilibrium with wildtype CYP2C8*1 and CYP2C9*1 alleles, which effectively makes it a determinant for a haplotype exhibiting an efficient CYP2C substrate metabolism.

CYP2D6 polymorphism in relation to tramadol metabolism: a study of faroese patients.

Several studies have demonstrated the impact of CYP2D6 polymorphism on the pharmacokinetics of tramadol. However, the relationship between the O-demethylation of tramadol and O-desmethyltramadol (M1) and CYP2D6 activity has not previously been investigated with tramadol in multimedicated outpatients under steady-state conditions. Hence, the aim of this study was to determine if the well documented pharmacokinetics of tramadol regarding CYP2D6 could be verified in a study including 88 multimedicated Faroese patients, treated with tramadol at steady-state conditions. Further, the study aimed to investigate whether the previously observed frequency of CYP2D6 poor metabolizers (PMs) in the Faroese, which was shown to be double that of other Europeans, was evident in a patient group medicated with a CYP2D6 substrate. The patients were CYP2D6-phenotyped by the intake of sparteine, followed by urine collection over 12 hours. Sparteine and its metabolites were assayed by gas chromatography. Genotype analyses for the CYP2D6 3, 4, 6, and 9 alleles were performed by polymerase chain reaction and Taqman technology. Plasma and urinary concentrations of (+/-)-tramadol and (+/-)-M1 were determined by high-performance liquid chromatography. With use of CYP2D6 phenotyping, 10 patients (11.5% [95% confidence interval (CI), 5.7-20.1%]) were classified as CYP2D6 PMs, and 8 (9.3% [95% CI, 4.1-17.3%]) of these were genotyped as CYP2D6 PMs. The PM frequency was not statistically significantly higher than that in other European populations (7%-10%). The concentrations of (+)-M1 when corrected for dose (nM/mg) and the (+)-M1/(+)-tramadol ratio were approximately 14-fold higher in the extensive metabolizers (EMs) than in the PMs. In conclusion, the impact of the CYP2D6 polymorphism on the pharmacokinetics of tramadol was clearly demonstrated in a group of multimedicated patients treated with tramadol under steady-state conditions. Further, the frequency of PMs was not higher than that in other European populations, as previously shown in different Faroese groups, possibly because of discontinued tramadol treatment in Faroese patients who were PMs.

Impact of dietary exposure to food contaminants on the risk of Parkinson's disease.

This study aimed to investigate the association of Parkinson's disease (PD) with dietary exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg) in a community with increased exposure levels. A total of 79 clinically verified idiopathic PD cases and 154 controls matched by sex and age were examined in this case-control study in the Faroe Islands. Blood and hair samples were collected and a questionnaire recorded lifetime information on residence, dietary habits, smoking history, and occupational exposure to solvents, pesticides, and metals. Both unconditional and conditional logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI) in regard to relevant exposure variables. Increased ORs for dietary intakes of whale meat and blubber during adult life were statistically significant. The ORs for occupational exposure to solvents, pesticides and metals also suggested an increased risk for PD. Current serum concentrations of summation operator PCB and related contaminants suggested slightly increased ORs, although only beta-hexachlorocyclohexane (beta-HCH) was statistically significant. Increased intake of whale meat and blubber in adult life was significantly associated with PD, thus suggesting a positive association between previous exposure to marine food contaminants and development of PD.

Genetic predisposition to Parkinson's disease: CYP2D6 and HFE in the Faroe Islands.

OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154 controls in the Faroe Islands. Genotyping for the 'CYP2D6*3, *4, *6 and *9' alleles and for the C282Y and H63D mutations were performed by real-time polymerase chain reaction before Taqman assessment. RESULTS: The frequency of CYP2D6 poor metabolizers among the patients was not higher compared with the frequency found in the control group (chi2 test, P=0.86). The odds ratio was 0.92 (95% confidence interval: 0.44-1.90). Neither was a difference in HFE genotype or allele frequencies found between the patients and the controls, and the C282Y and H63D mutation carrier frequencies did not reveal any difference (chi2 test, P=0.50 and 0.60, respectively). CONCLUSION: This study does not support an association between PD and mutations of the CYP2D6 and HFE genes, although a weak association cannot be excluded. The high frequency of PD in the Faroes is most likely the result of interactions between multiple genetic and environmental factors, still to be identified.

The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population.

AIM: To determine the frequency of CYP2D6 poor metabolizers (PMs) in a Faroese patient group medicated with amitriptyline (AT) and to investigate plasma concentrations of AT and metabolites in relation to CYP2D6. METHODS: CYP2D6 phenotype and genotype were determined in 23 Faroese patients treated with AT. Plasma concentrations of AT and metabolites were determined by high-performance liquid chromatography and investigated in relation to CYP2D6 activity. RESULTS: Of the 23 patients phenotyped and genotyped, five (22%) (95% confidence interval 7.5, 43.7) were CYP2D6 PMs. No difference was found in AT daily dosage between PMs (median 25 mg day(-1); range 5-80) and extensive metabolizers (EMs) (median 27.5 mg day(-1); range 10-100). The (E)-10-OH-nortriptyline (NT)/dose concentrations were higher in EMs than in PMs and the NT/(E)-10-OH-NT and AT/(E)-10-OH-AT ratios were higher in PMs compared with EMs. The log sparteine metabolic ratio correlated positively with the NT/(E)-10-OH-NT ratio (r(s) = 0.821; P < 0.0005) and the AT/(E)-10-OH-AT ratio (r(s) = 0.605; P < 0.006). CONCLUSION: A high proportion of CYP2D6 PMs was found in a Faroese patient group medicated with AT. However, similar doses of AT and concentrations of AT and NT were noted in EMs and PMs, probably due to varying doses and indications for AT treatment.

Polychlorinated biphenyl (PCB) induction of CYP3A4 enzyme activity in healthy Faroese adults.

The CYP3A4 enzyme is, along with other cytochrome P450 enzymes, involved in the metabolism of environmental pollutants and is highly inducible by these substances. A commercial polychlorinated biphenyl (PCB) mixture, 1,1,1,-trichloro-2-(o-chlorophenyl), 2-(p'-chlorophenyl)ethane (o,p'-DDT) and 1,1,-dichloro-2,2-bis (p-chlorophenyl)ethene (p,p'-DDE) are known to induce CYP3A4 activity through activation of nuclear receptors, such as the pregnane X receptor. However, this induction of CYP3A4 has not yet been investigated in humans. Thus, the aim of the study was to determine the variability of the CYP3A4 phenotype in regard to increased concentrations of PCBs and other persistent organohalogen pollutants (POPs) in healthy Faroese adults. In 310 randomly selected Faroese residents aged 18-60 years, the CYP3A4 activity was determined based on the urinary 6beta-hydroxycortisol/cortisol (6beta-OHC/FC) ratio. POP exposures were assessed by measuring their concentrations in serum lipid. The results showed a unimodal distribution of the 6beta-OHC/FC ratio with values ranging from 0.58 to 27.38. Women had a slightly higher 6beta-OHC/FC ratio than men (p=0.07). Confounder-adjusted multiple regression analysis showed significant associations between 6beta-OHC/FC ratios and summation PCB, PCB-TEQ and p,p'-DDE, o,p'-DDT and HCB, respectively, but the associations were statistically significant for men only.

Caffeine N3-demethylation (CYP1A2) in a population with an increased exposure to polychlorinated biphenyls.

OBJECTIVE: To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity. METHODS: In 305 randomly selected Faroese residents aged 18-60 years, the CYP1A2 activity was determined following oral intake of a caffeine dose and subsequent determination of the urinary metabolites and calculation of the caffeine metabolic ratio (CMR). PCB exposure was assessed by measuring the serum concentration of major congeners. RESULTS: The CYP1A2 phenotype distribution was unimodal. The CMR was significantly higher both in smoking men and in smoking women, independent of oral contraceptive use, as compared with non-smokers. Among non-smokers, the CMR was significantly higher in women not using oral contraceptives than in those using oral contraceptives; a similar difference could not be established among smokers. The CMR appeared higher in men than in women, but stratified analyses confirmed a significant sex-related difference only among smokers not using oral contraceptives. Overall, the mean CMR in Faroese was significantly higher compared with the mean CMR in Danish historical controls. No association was found with PCB exposure and individual PCB congeners, except for one of three dioxin-like congeners, in confounder-adjusted multiple regression analyses. CONCLUSION: The CYP1A2 phenotype in Faroese residents was unimodally distributed and showed the inducing effect of smoking and the inhibiting effect of use of oral contraceptives, but a sex-related difference was not apparent after confounder adjustment. There was no statistically significant association between CMR and PCB exposure.

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

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; chi(2) test) among the Faroese than in other European populations (7.4%). Genotype analyses for the CYP2D6*3, *4, *6 and *9 alleles were performed using real-time polymerase chain reaction (PCR) (TaqMan, Foster City, CA, USA), 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 means of 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 twofold higher among the Faroese population than 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.