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PubMed1997

CYP2D6-related oxidation polymorphism in a Canadian Inuit population.

The xenobiotic oxidation polymorphism associated with cytochrome P450 2D6 (CYP2D6) was investigated in 152 genetically related and unrelated healthy Inuit subjects living in the High Arctic of eastern Canada. Phenotyping was based on HPLC determination of the CYP2D6-related dextromethorphan metabolic ratio in overnight urine samples after oral administration of 30 mg dextromethorphan hydrobromide. The log metabolic ratio was bimodally distributed, with three subjects classified as poor metabolizers (PMs). In subjects unrelated in the first degree, the incidence of the PM phenotype was 3 of 90 or 3.3%. PCR-based analyses of DNA for variants of the CYP2D6 gene demonstrated that the PMs of dextromethorphan had the defective allele CYP2D6*4. The estimated frequency of the CYP2D6*4 allele was 0.067-0.083, which is lower than the frequency in Caucasians but higher than the frequency in Oriental populations. The CYP2D6*3 and the CYP2D6*6 alleles were not detected in the Inuit population. The CYP2D6*10 allele was present in only four unrelated subjects, classified as extensive metabolizers (EMs), resulting in an estimated allele frequency of 0.022, which is much lower than in Oriental populations. This study demonstrated the existence of the CYP2D6 polymorphism in Canadian Inuit, while the frequencies of allelic variants of CYP2D6 point to the uniqueness of this population. Several important therapeutic drugs that are being prescribed in Arctic communities will have altered pharmacokinetics in PMs of CYP2D6.

Adolescent↗
PubMed1998

NAD(P)H:quinone oxidoreductase: polymorphisms and allele frequencies in Caucasian, Chinese and Canadian Native Indian and Inuit populations.

NAD(P)H:quinone oxidoreductase (NQO1) catalyses the two-electron reduction of quinone compounds. NQO1 is involved in the reductive bioactivation of cytotoxic antitumour quinones such as mitomycin C, but also plays a protective role against the carcinogenicity and mutagenicity of quinones, their precursors and metabolites. Three alleles have been identified in the human population: the functional Arg139/Pro187 allele (which we have termed NQO1*1); the nonfunctional allele Arg139/Ser187 (NQO1*2) and the Trp139/Pro187 allele (NQO1*3), which is associated with a diminished activity. We applied polymerase chain reaction-based genotyping assays to characterize interethnic variability in the frequency of NQO1 alleles in Caucasian (n = 575), Canadian Native Indian (n = 110), Canadian Inuit (n = 83) and Chinese (n = 86) populations. The NQO1*2 allele was found at significantly higher frequencies in Chinese (0.49) and Native North American populations (Inuit 0.46; Canadian Native Indians 0.40) compared with Caucasians (0.16). The NQO1*3 allele was not observed in Inuit individuals, and occurred at a lower frequency than the NQO*2 allele in Caucasians (0.05), Chinese (0.04) and Canadian Native Indians (0.01). Our results predict that a greater proportion of Orientals and related ethnic groups lack, or have reduced, NQO activity relative to Caucasians. Affected individuals may not only exhibit resistance to quinone-based cancer therapy because of a decreased production of cytotoxic drug metabolites, but may also be more susceptible to toxicities associated with toxicants.

Alleles↗
PubMed1983

Paraoxonase phenotype distribution in Canadian Indian and Inuit populations.

Test objects were the sera of 57 North American Indian and 67 Inuit subjects. The paraoxon-hydrolyzing activity, a, was determined, as well as the paraoxonase-phenotyping ratio, c/b, a ratio designating enzyme activation by Na+ in the presence of Ca2+. The values of c/b were clearly bimodally distributed. Location of the modes and of the antimodal gap were in perfect agreement with the results previously obtained on Caucasian sera. This allowed us to retain the criterion which had been already established in the study of Caucasians, i.e., c/b less than 1.5 = "low-activity" phenotype, and c/b greater than 1.5 = "high-activity" phenotype. The proportions of individuals in each mode differed, however. In Caucasians, the frequency of the "low-activity" phenotype had been estimated as 51.2%. In Indians and Inuits, it was 7.0% and 6.0%, respectively. Independent of phenotype, Indian and Inuit sera displayed lower paraoxon-hydrolyzing activity than did Caucasian sera.

Aryldialkylphosphatase↗
PubMed1996

Spondylolysis of the sacrum in Alaskan and Canadian Inuit skeletons.

Spondylolysis of the lower back, particularly that involving the isthmus between the superior and inferior articular processes (pars interarticularis), is generally attributed to stress fracturing caused by movement of the affected vertebra relative to the vertebra below. The finding of isthmic spondylolysis in the first vertebra of a fused sacrum is thus unusual and requires explanation. Although unrepresented in the clinical literature, sacral spondylolysis has been reported for archaeological specimens and appears to be especially prevalent in North American Inuit. A study of 373 Inuit sacra from Alaska and Canada produced 16 examples of spondylolysis (eight from each area). All but one of the affected individuals were male, and nearly all were young adults, many between 18 and 20 years of age. All cases of sacral spondylolysis observed in this study were judged to have resulted from stress fracturing that occurred while S1 was still unfused, and most appear to have been in the process of healing, following fusion of S1 with S2, when death occurred. The high frequency observed in these people is attributed to unusual stresses becoming concentrated in the lower back of adolescent males due to such activities as weight lifting, wrestling, kayak paddling, and harpooning, combined with, and perhaps even contributing to, delayed maturation (S1-S2 fusion) of the sacrum.

Adolescent↗
PubMed1989

Three-dimensional analysis of the maxillary first molar crowns of Canadian Inuit.

The maxillary first molar crowns of 48 male and 38 female Canadian Inuit (Eskimos) were analyzed three-dimensionally by using moiré contourography methods. Cusp heights were significantly higher in males while the mesial and distal marginal ridges were more proximally placed in males. The metacone and the oblique ridge appeared to be better developed in the males. Comparison of the present results with published results for Dutch and Japanese indicated that the Japanese and Inuit had lower cusps that were more widely spaced than the Dutch. Correlation coefficients suggest that height measurements were positively correlated as were linear measurements. However, there were few significant correlations between height and linear determinations, suggesting that the development of the "width" of a crown is nearly independent of the development of the height of the cusps and crown.

Canada↗
PubMed2003

Cancer in Greenlandic Inuit 1973-1997: a cohort study.

The increasing westernization of the Arctic countries may influence the very particular cancer profile of these populations. Our objective was to investigate the development in cancer incidence from 1973 to 1997 in a large and well-defined Inuit population in Greenland. Greenland is part of the Danish Kingdom, and population statistics covering both countries are available from the same registry resource. Data from the Danish Civil Registration System and from the Danish Cancer Registry were used to calculate age-standardized cancer incidence rates for the periods 1973-1987 and 1988-1997 for persons born in Greenland. Using rates for Denmark, sex-specific standardized incidence ratios (SIRs) for 1988-1997 were calculated. Furthermore, age- and sex-specific incidence rates in the 2 periods were calculated for selected cancers. Total cancer incidence increased from 248.5 to 277.9 per 100,000 person-years in men and from 269.4 to 302.2 per 100,000 person-years in women. The incidence of lung, stomach, breast and colon cancer increased, whereas the incidence of cervical cancer decreased. Compared to the Caucasian population in Denmark, high SIRs were found for cancers of the nasopharynx, salivary gland, esophagus, stomach and cervix and low SIRs for testis, bladder, prostate, breast and hematologic cancers. Overall cancer incidence among Greenlandic Inuit is increasing as a result of increases in several cancers that are common in Western populations. A significant increase in the incidence of stomach cancer in both sexes, which contrasts global trends for this cancer, warrants further investigation.

Cohort Studies↗
PubMed1996

The apolipoprotein E polymorphism in Greenland Inuit in its global perspective.

Apolipoprotein E (apoE) genotypes were determined in Inuit population samples from Nuuk on the south-west coast of Greenland (n = 100) and from the Ammassalik region on the south-east coast (n = 78). The epsilon 2 allele was absent in the latter sample, and the epsilon 4 allele frequency was relatively high, about 23%. As in most other populations, mean plasma lipoprotein-related variables, except high-density lipoprotein (HDL) cholesterol, were higher in both Inuit men and women with epsilon 4 than in epsilon 3 epsilon 3 genotypes (P < 0.05 for triglycerides in men, and for non-HDL cholesterol and apolipoprotein B in women). The estimated apoE allele frequencies were combined with data from other studies of aboriginal peoples to outline a world map of apoE allele frequencies. A recent study of non-human primates suggests that epsilon 4, and not epsilon 3, is the ancestral allele in humans and we have used the map to generate additional hypotheses regarding the history of the apoE polymorphism in humans.

Alleles↗
PubMed1992

Inuit foods and diet: a preliminary assessment of benefits and risks.

Traditional Inuit foods are contaminated with chemical residues from industrial and other activities around the world. The intake of polychlorinated biphenyls (PCBs) and polychlorinated camphenes (PCCs) exceeds the 'tolerable daily intake' (TDI) for many consumers. The implications of long term contaminant intake, even for single contaminants, are not known and will be difficult or impossible to determine in the foreseeable future. Traditional foods form a substantial part of the Inuit diet and are a major source of energy and essential nutrients. Available alternative imported foods are nutritionally inferior and substitution may lead to nutritional deficiencies and associated risks to health and to the social and cultural life of Arctic communities.

Adolescent↗
PubMed1988

Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods.

The fatty acid composition of mature breast milk total lipids was analysed in milk from Inuit women living in a small Arctic community. Long-chain n-3 fatty acids were higher than in comparable samples from Vancouver residents. The data suggest that secretion of n-3 fatty acids in milk is influenced by the dietary intake of the lactating woman. The levels of these fatty acids in Inuit milk approximate those reported for the diet fat of adult Eskimo, and which have been associated with reduced plasma cholesterol levels and death from coronary heart disease.

British Columbia↗
PubMed1994

Epidemic Escherichia coli O157:H7 gastroenteritis and hemolytic-uremic syndrome in a Canadian inuit community: intestinal illness in family members as a risk factor.

OBJECTIVE: To evaluate risk factors for childhood hemolytic-uremic syndrome (HUS) and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection. DESIGN: Case-control study. SETTING: Remote Inuit community of Arviat in northern Canada. PARTICIPANTS: Of the 565 Arviat residents less than 15 years of age, 19 had HUS and 65 more had E. coli O157:H7 gastroenteritis. The 19 children with HUS were compared with 19 age- and gender-matched children with uncomplicated E. coli O157:H7 gastroenteritis, and both HUS and gastroenteritis patients were compared with 19 healthy control subjects. INTERVENTIONS: Questionnaire administered face-to-face to parents of participants in the home. MAIN OUTCOME MEASURES: Rates of exposure to foods, travel, sources of water, and gastrointestinal illness in family members. RESULTS: Patients with HUS and those with uncomplicated E. coli O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7 days before the onset of gastrointestinal symptoms, children with HUS and those with uncomplicated gastroenteritis were more likely to have been exposed to a family member with diarrhea than were the healthy control subjects (odds ratio = 9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p < 0.01). Undercooked ground meat and foods traditionally consumed by the Inuit were not implicated as risk factors in E. coli O157:H7 infection. CONCLUSIONS: These findings emphasize the potential for extensive intrafamilial transmission of verotoxin-producing E. coli once infection is introduced into certain communities.

Case-Control Studies↗
PubMedDate not supplied

PCBs and dioxin-like compounds in plasma of adult Inuit living in Nunavik (Arctic Quebec).

Inuit people residing in the Arctic are unusually exposed to organochlorines through their traditional diet which includes large quantities of sea mammal fat. Recently, 499 Inuit adults from Nunavik (Arctic Quebec) participated in a large health survey and donated a blood sample for organochlorine and heavy metal analysis. Twenty pooled plasma samples were formed, each made of individual samples from the same age group, sex, and region of residence, to allow for dioxin-like compound determination. The mean total concentration of PCBs and dioxin-like compounds (the latter expressed in 2,3,7,8-TCDD toxic equivalents) were respectively 4.1 mg/kg lipids and 184.2 ng/kg lipids, compared to 0.13 mg/kg lipids and 26.1 ng/kg lipids for three control pooled plasma samples from Southern Quebec. Total PCBs and dioxin-like compound concentrations were strongly correlated (r = 0.98; p < 0.0001), increased with age and were greater in men than in women. Although the body burdens of PCBs and dioxin-like compounds are close to those which induced adverse health effects in laboratory animals, dietary benefits from the sea-food based diet still outweigh the hypothetical health risks.

Adult↗
PubMed1997

Homocysteine in Greenland Inuits.

Patients with homozygous homocystinuria are at greatly increased risk for development of atherosclerosis and thrombosis (1). Elevated plasma levels of homocysteine (HCY) are caused by reduced enzymatic catabolism or reduced enzymatic remethylation of HCY, due to either hereditary enzyme defects or to nutritional deficiencies of vitamins functioning as cofactors. However, several recent studies have suggested that persons with mildly elevated plasma levels of HCY also are at increased risk for coronary heart disease. (2-4). There are some indications that dietary n-3 polyunsaturated fatty acids (PUFAs) may offer protection against coronary heart disease (5-6). Several mechanisms may be involved, including beneficial effects of n-3 PUFAs on plasma lipids, platelet and leukocyte reactivity, blood pressure and vasoreactivity (7). Interestingly, Olszewski el al. recently found HCY-levels to be lowered 36% in 15 type IIa or IIb hyperlipemic men by n-3 PUFA supplementation. A possible beneficial effect of n-3 PUFA on the incidence of coronary heart disease was initially suggested from studies in Greenland Inuits by our group (8). We therefore investigated plasma levels of homocysteine in a group of traditionally living Greenland Inuits with a diet consisting mainly of marine food and with a very high content of n-3 PUFAs.

Adult↗
PubMed1999

Otitis media in Inuit children in the Eastern Canadian Arctic--an overview--1968 to date.

Clinical observations made on the Inuit in the Eastern Canadian Arctic during the past three decades support that the current high prevalence of chronic otitis media among their children is a relatively new phenomenon. It is a social/economic disease related to their urbanization that occurred following World War II when the vast majority of the Inuit abandoned their isolated nomadic way of life and moved into permanent settlements. The disease, in a great many, runs a natural course with spontaneous healing. There is evidence that as the new millennium approaches the prevalence of the disease among the children is decreasing.

Canada↗
PubMed2002

Cultural change and mental health in Greenland: the association of childhood conditions, language, and urbanization with mental health and suicidal thoughts among the Inuit of Greenland.

In Greenland, the rapid sociocultural change of the last 50 years has been paralleled by an epidemiological transition characterized by a reduction in infectious diseases, an increase in cancer and cardiovascular diseases, and an increased prevalence of mental health problems. During 1993-94 and 1997-98, two health interview surveys were conducted among Inuit in Greenland and Inuit migrants in Denmark. The response rates were 71 and 55%. Information on mental health was obtained from 1388 and 1769 adults. As indicators of mental health, the prevalence of potential psychiatric cases according to the General Health Questionnaire (GHQ-12) and the prevalence of suicidal thoughts were studied in relation to childhood residence and father's occupation, current residence, and language. The statistical methods included logistic regression and graphical independence models. The results indicated a U-shaped association in Greenland of GHQ-cases with age and a high prevalence of suicidal thoughts among young people; a low prevalence of GHQ-cases among those who were bilingual or spoke only Danish; and a high prevalence of suicidal thoughts among migrants who grew up in Denmark and among residents of the capital of Greenland. In Greenland, women were more often GHQ-cases and had suicidal thoughts more often than men. The association between language and GHQ-cases is presumed to operate through socioeconomic factors. It is necessary to modify the common notion that rapid societal development is in itself a cause of poor mental health: as a result of successful integration into the modern Greenlandic society, some population groups have better mental health compared to other groups.

Acculturation↗
PubMed2001

Glaucoma in East Greenlandic Inuit--a population survey in Ittoqqortoormiit (Scoresbysund).

PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG) in an isolated Greenlandic Inuit community and to examine the anatomical risk factors for this disease. METHODS: All individuals aged > or =40 years were examined. Visual acuity, refractive error, anterior chamber depth (ACD), intraocular pressure (IOP), gonioscopy, and optic disc characteristics were recorded. RESULTS: Seventy-nine individuals (65% response rate) were examined. Mean IOP was 12.0 mmHg. ACD was shallow and decreased with age and hypermetropia. ACD was deeper than observed in the same community in 1981 and another East Greenland population in 1970. Two subjects had definite PACG (2.5 %). CONCLUSION: This is the first study to use applanation tonometry in a Greenland population and confirms a low IOP as found in other populations of Inuit and Mongolians. ACD measured in 1998 was deeper than in 1981 in the same community which may represent a cohort effect indicating a secular change.

Adult↗
PubMed2000

The associations of a marine diet with plasma lipids, blood glucose, blood pressure and obesity among the inuit in Greenland.

OBJECTIVE: To analyse the associations between the intake of fish and marine mammals and risk factors for cardiovascular disease, ie lipid profile, fasting blood glucose, blood pressure and obesity, in a population whose average consumption of n-3 fatty acids is high compared with Western countries. DESIGN: Information was obtained from a population survey in Greenland: interview data, clinical data and fasting blood samples were obtained from a random sample of Inuit from three towns and four villages. SUBJECTS: Two-hundred and fifty-nine adult Inuit (74% of the sample). RESULTS: Marine diet was positively associated with serum high-density lipoprotein (HDL) and blood glucose and inversely with very-low-density lipoprotein (VLDL) and triglyceride. Association with low-density lipoprotein (LDL), diastolic and systolic blood pressure, waist-hip ratio and body mass index were inconsistent and not statistically significant. The pattern was similar within groups with low, medium and high consumption of marine food. CONCLUSIONS: There are statistically significant associations between the consumption of marine food and certain lipid fractions in the blood also in this population with a very high average intake of marine food. The observation that blood glucose is positively associated with marine diet in a population survey is new and should be repeated. There was good agreement between the results for the reported consumption of seal and those for the biomarkers. SPONSORSHIP: The study was financially supported by the Greenland Home Rule, Directorate of Health and Research, the Commission for Scientific Research in Greenland, and the Danish Medical Research Council.

Adolescent↗
PubMed2002

Allergen sensitization and allergen exposure in Greenlander Inuit residing in Denmark and Greenland.

The aim of this study was to estimate the prevalence of allergic sensitization and possible risk factors in a genetically homogenous Inuit population living under widely differing climatic and cultural conditions. A written questionnaire and skin prick test for 10 aeroallergens were obtained from 1119 adult Greenlanders residing in Denmark, Nuuk (main city in Southern Greenland) and Uummannaq (rural settlement in Northern Greenland). Allergen exposure was assessed by pollen counts, questions on pet keeping and counts of house dust mites in dust samples. The overall prevalence of at least one positive skin prick test was 22.8% in Denmark, 10.6% in Nuuk, and 6.4% in Uummannaq. In Denmark, the total birch pollen counts were 40-1000 times higher compared to Nuuk, whereas the grass pollen count was 13-30 times higher in Denmark compared to Nuuk. Dogs were held indoor with a similar frequency in Denmark and Nuuk, but much less frequently in Uummannaq. In Denmark, house dust mites were found in 72% of house holds (>10/0.1 g dust). Less than 15% of households in Greenland had measurable levels of house dust mites. The prevalence of sensitization to aeroallergens in Inuit Greenlanders differed significantly between Denmark, Nuuk and Uummannaq. These findings correlated with the observed differences in population allergen exposure in the three regions. Furthermore, differences in lifestyle factors such as educational level, stress and ethnic self-identification seemed to be associated with the risk of allergic sensitization in Greenland.

Adolescent↗
PubMed2005

Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity.

BACKGROUND: Persistent organochlorine pollutants (POP), such as polychlorinated biphenyls (PCB) and dichlorodiphenyldichloroethylene (p, p'-DDE), are widely found in the environment and considered potential endocrine-disrupting compounds (EDC). Their impact on male fertility is still unknown. METHODS: To explore the hypothesis that POP is associated with altered sperm chromatin integrity, a cross-sectional study involving 707 adult males (193 Inuits from Greenland, 178 Swedish fishermen, 141 men from Warsaw, Poland, and 195 men from Kharkiv, Ukraine) was carried out. Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), as a proxy of the total PCB burden, and of p,p'-DDE were determined. Sperm chromatin structure assay (SCSA) was used to assess sperm DNA/chromatin integrity. RESULTS: We found a strong and monotonically increasing DNA fragmentation index with increasing serum levels of CB-153 among European but not Inuit men, reaching a 60% higher average level in the highest exposure group. No significant associations were found between SCSA-derived parameters and p, p'-DDE serum concentrations. CONCLUSION: These results suggest that human dietary PCB exposure might have a negative impact on the sperm chromatin integrity of adult males but additional issues, including differences in the genetic background and lifestyle habits, still need to be elucidated.

Adolescent↗