Allelic diversity of the pharmacogene CYP2D6 in New Zealand Maori and Pacific peoples.

The enzyme cytochrome P450 2D6 (CYP2D6) metabolises approximately 25% of commonly prescribed drugs, including analgesics, anti-hypertensives, and anti-depressants, among many others. Genetic variation in drug metabolising genes can alter how an individual responds to prescribed drugs, including predisposing to adverse drug reactions. The majority of research on the CYP2D6 gene has been carried out in European and East Asian populations, with many Indigenous and minority populations, such as those from Oceania, greatly underrepresented. However, genetic variation is often population specific and analysis of diverse ethnic groups can reveal differences in alleles that may be of clinical significance. For this reason, we set out to examine the range and frequency of CYP2D6 variants in a sample of 202 Maori and Pacific people living in Aotearoa (New Zealand). We carried out long PCR to isolate the CYP2D6 region before performing nanopore sequencing to identify all variants and alleles in these samples. We identified twelve variants which have previously not been reported in the PharmVar CYP2D6 database, three of which were exonic missense variations. Six of these occurred in single samples and one was found in 19 samples (9.4% of the cohort). The remaining five variants were identified in two samples each. Identified variants formed twelve new CYP2D6 suballeles and four new star alleles, now recorded in the PharmVar database. One striking finding was that CYP2D6*71, an allele of uncertain functional status which has been rarely observed in previous studies, occurs at a relatively high frequency (8.9%) within this cohort. These data will help to ensure that CYP2D6 genetic analysis for pharmacogenetic purposes can be carried out accurately and effectively in this population group.

New Zealand postgraduate medical training by distance for Pacific Island country-based general practitioners: a qualitative study.

Introduction New Zealand health training institutions have an important role in supporting health workforce training programmes in the Pacific Region. Aim To explore the experience of Pacific Island country-based doctors from the Cook Islands, Niue, and Samoa, studying in New Zealand's University of Otago distance-taught Rural Postgraduate programme. Methods Document analysis (16 documents) was undertaken. Eight semi-structured interviews were conducted with Pacific Island country-based students. Thematic analysis of the interviews was undertaken using the framework method. The two data sources were analysed separately, followed by a process to converge and corroborate findings. Results For Pacific Island countries with no previous option for formal general practice training, access to a recognised academic programme represented a milestone. Immediate clinical relevance and applicability of a generalist medical curriculum with rural remote emphasis, delivered mainly at a distance, was identified as a major strength. Although technologies posed some issues, these were generally easily solved. The main challenges identified related to the provision of academic and other support. Traditional university support services and resources were campus focused and not always easily accessed by this group of students who cross educational pedagogies, health systems and national borders to study in a New Zealand programme. Study for individuals worked best when it was part of a recognised and supported Pacific in-country training pathway. Discussion The University of Otago's Rural Postgraduate programme is accessible, relevant and achievable for Pacific Island country-based doctors. The programme offers a partial solution for training in general practice for the Pacific region. Student experience could be improved by tailoring and strengthening support services and ensuring their effective delivery.

Higher prevalence of left ventricular hypertrophy in two Maori cohorts: findings from the Hauora Manawa/Community Heart Study.

OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of mortality in New Zealand with a disproportionate burden of disease in the Maori population. The Hauora Manawa Project investigated the prevalence of cardiovascular risk factors and CVD in randomly selected Maori and non-Maori participants. This paper reports the prevalence of structural changes in the heart. METHODS: A total of 252 rural Maori, 243 urban Maori; and 256 urban non-Maori underwent echocardiography to assess cardiac structure and function. Multivariable logistic regression was used to determine variables associated with heart size. RESULTS: Left ventricular (LV) mass measurements were largest in the rural Maori cohort (183.5,sd 61.4), intermediate in the urban Maori cohort (169.7,sd 57.1) and smallest in the non-Maori cohort (152.6,sd 46.7; p<0.001). Similar patterns were observed for other measurements and indexation had no impact. One-third (32.3%) met the gender-based ASE criteria for LV hypertrophy (LVH) with higher prevalence in both Maori cohorts (highest in the rural cohort). There were three significant predictors of LVH: rural Maori (p=0.0001); age (p<0.0001); and gender (p=0.0048). CONCLUSION: Structural and functional heart abnormalities are more prevalent in Maori compared to non-Maori, and especially rural Maori. Early identification should lead to better management, ultimately improving life expectancy and quality of life.

A cohort study comparing cardiovascular risk factors in rural Maori, urban Maori and non-Maori communities in New Zealand.

OBJECTIVES: To understand health disparities in cardiovascular disease (CVD) in the indigenous Maori of New Zealand, diagnosed and undiagnosed CVD risk factors were compared in rural Maori in an area remote from health services with urban Maori and non-Maori in a city well served with health services. DESIGN: Prospective cohort study. SETTING: Hauora Manawa is a cohort study of diagnosed and previously undiagnosed CVD, diabetes and risk factors, based on random selection from electoral rolls of the rural Wairoa District and Christchurch City, New Zealand. PARTICIPANTS: Screening clinics were attended by 252 rural Maori, 243 urban Maori and 256 urban non-Maori, aged 20-64 years. MAIN OUTCOME MEASURES: The study documented personal and family medical history, blood pressure, anthropometrics, fasting lipids, insulin, glucose, HbA1c and urate to identify risk factors in common and those that differ among the three communities. RESULTS: Mean age (SD) was 45.7 (11.5) versus 42.6 (11.2) versus 43.6 (11.5) years in rural Maori, urban Maori and non-Maori, respectively. Age-adjusted rates of diagnosed cardiac disease were not significantly different across the cohorts (7.5% vs 5.8% vs 2.8%, p=0.073). However, rural Maori had significantly higher levels of type-2 diabetes (10.7% vs 3.7% vs 2.4%, p<0.001), diagnosed hypertension (25.0% vs 14.9% vs 10.7%, p<0.001), treated dyslipidaemia (15.7% vs 7.1% vs 2.8%, p<0.001), current smoking (42.8% vs 30.5% vs 15.2%, p<0.001) and age-adjusted body mass index (30.7 (7.3) vs 29.1 (6.4) vs 26.1 (4.5) kg/m(2), p<0.001). Similarly high rates of previously undocumented elevated blood pressure (22.2% vs 23.5% vs 17.6%, p=0.235) and high cholesterol (42.1% vs 54.3% vs 42.2%, p=0.008) were observed across all cohorts. CONCLUSIONS: Supporting integrated rural healthcare to provide screening and management of CVD risk factors would reduce health disparities in this indigenous population.

Community screening for cardiovascular risk factors and levels of treatment in a rural Maori cohort.

OBJECTIVES: To document levels of cardiovascular disease (CVD), diagnosed and undiagnosed risk factors and clinical management of CVD risk in rural Maori. METHODS: Participants (aged 20-64 years), of Maori descent and self-report, were randomly sampled to be representative of age and gender profiles of the community. Screening clinics included health questionnaires, fasting blood samples, blood pressure and anthropometric measures. Data were obtained from participants' primary care physicians regarding prior diagnoses and current clinical management. New Zealand Cardiovascular Guidelines were used to identify new diagnoses at screening and Bestpractice electronic-decision support software used to estimate 5-year CVD risk. RESULTS: Mean age of participants (n=252) was 45.7 ± 0.7, 8% reported a history of cardiac disease, 43% were current smokers, 22% had a healthy BMI, 30% were overweight and 48% obese. Hypertension was previously diagnosed in 25%; an additional 22% were hypertensive at screening. Dyslipidaemia was previously diagnosed in 14% and an additional 43% were dyslipidaemic at screening. Type-2 diabetes was previously diagnosed in 11%. Glycaemic control was achieved in only 21% of those with type-2 diabetes. Blood pressure and cholesterol were above recommended targets in more than half of those with diagnosed CVD risk factors. CONCLUSIONS: High levels of diagnosed and undiagnosed CVD risk factors, especially hypertension, dyslipidaemia and diabetes were identified in this rural Maori community. IMPLICATIONS: There is a need for opportunistic screening and intensified management of CVD risk factors in this indigenous population group.

A Kaupapa Maori approach to a community cohort study of heart disease in New Zealand.

OBJECTIVE: To report the processes and protocols that were developed in the design and implementation of the Hauora Manawa Project, a cohort study of heart disease in New Zealand and to report the participation at baseline. METHODS: This study utilised application of a Kaupapa Maori Methodology in gaining tribal and health community engagement, design of the project and random selection of participants from territorial electoral rolls, to obtain three cohorts: rural Maori, urban Maori and urban non-Maori. Logistic regression was used to model response rates. RESULTS: Time invested in gaining tribal and health community engagement assisted in the development and design of clear protocols and processes for the study. Response rates were 57.6%, 48.3% and 57.2%. Co-operation rates (participation among those with whom contact was established) were 74.7%, 66.6% and 71.4%. CONCLUSIONS: Use of electoral rolls enables straightforward sampling but results in low response rates because electors have moved. Co-operation rates highlight the acceptability of this research project to the participants; they indicate the strength of Kaupapa Maori Methodologies in engaging Maori participants and community. IMPLICATIONS: This study provides a model for conducting clinical/biomedical research projects that are compatible with cultural protocols and methodologies, in which the primary aim of the research was Maori health gain.