Variable association between genetic variation in the CYP7 gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -278A in the CYP7 gene, which encodes cholesterol 7-alpha hydroxylase, was previously reported to be associated with reduced plasma low density lipoprotein (LDL) cholesterol concentration. We tested for association of CYP7-278A with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 594 Alberta Hutterites, 325 Ontario Oji-Cree and 190 Keewatin Inuit. The CYP7-278A allele frequencies in these three groups were 0.708, 0.466 and 0.490, respectively. The frequencies of CYP7-278A/A homozygotes were 0.481, 0.215 and 0.247, respectively. In the Hutterites, CYP7-278A was associated with reduced plasma HDL-cholesterol and apolipoprotein AI concentration. In the Oji-Cree, CYP7-278A was not significantly associated with any plasma lipoprotein trait. In the Inuit CYP7-278A was associated with elevated plasma total and LDL-cholesterol. There was no consistent relationship between the population mean plasma LDL-cholesterol concentration and the population CYP7-278A frequency. Our findings suggest that the common -278A promoter variant of CYP7 was inconsistently associated with variation in plasma LDL- and HDL-cholesterol in samples from three independent populations. The inconsistencies could be due to differences in genetic background or to unspecified environmental or genetic factors.

Absence of association between genetic variation in the LIPC gene promoter and plasma lipoproteins in three Canadian populations.

The promoter sequence variant -480T in the hepatic lipase gene (LIPC) has been shown to be significantly associated with low post-heparin hepatic lipase activity. Some studies have also found that the -480T variant is associated with elevation in plasma HDL cholesterol. We tested for associations of LIPC -480T with plasma lipoprotein traits in samples taken from three distinct Canadian populations: 657 Alberta Hutterites, 328 Ontario Oji-Cree and 210 Keewatin Inuit. Plasma HL activity was not available for analyses. The LIPC -480T allele frequencies in these three groups, respectively, were 0.219, 0.527 and 0.383, and the prevalence of LIPC -480T/T homozygotes was, respectively, 0.042, 0.274 and 0.167. No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index. There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency. Our findings are consistent with the idea that the common promoter variation in LIPC, which has been reported to be associated with variation in post heparin HL activity and HDL triglyceride concentration, is not always associated with variation in plasma HDL cholesterol concentration, possibly due to yet unspecified environmental or genetic factors.

Teaching quantitative and qualitative analysis to undergraduate students.

Data analysis preparation for undergraduate nursing students conventionally has consisted of a required statistics course and a brief discussion of analysis strategies within an introductory research course. For students to view inquiry as integral to their practice, it is imperative that data analysis be taught in a manner whereby it may be incorporated into their repertoire of skills for nursing inquiry. This article describes an interdisciplinary, introductory course in quantitative and qualitative analysis taught in the context of three requisite inquiry courses: knowledge development, nursing inquiry, and nursing research.

Association and linkage of LDLR gene variation with variation in plasma low density lipoprotein cholesterol.

The role of common variation in the low density lipoprotein (LDL) receptor gene (LDLR) as a determinant of variation in plasma LDL cholesterol in normolipidemic populations is not well established. To address this question, we used both association and linkage analysis to evaluate the relationship between plasma LDL cholesterol and genetic variation in LDLR and in three other candidate genes for lipoprotein metabolism, namely, APOE, PONI, and LPL. We studied a sample of 719 normolipidemic Alberta Hutterites, who comprised 1217 sib pairs. Variation in each of the four candidate genes was significantly associated with variation in plasma LDL cholesterol, but the average effects of the alleles were small. In contrast, sib pair analysis showed that only the LDLR gene variation was linked with variation in plasma LDL cholesterol (P = 0.026). Thus, the common LDLR gene variation was both associated with and linked to variation in plasma LDL cholesterol, suggesting that there is a functional impact of structural variation in LDLR on plasma LDL cholesterol in this study sample. However, the absence of linkage of variation in LDL cholesterol with the other three candidate genes, in particular APOE, is consistent with a lower sensitivity of linkage analysis compared with association analysis for detecting modest effects on quantitative traits. Attributes such as the genetic structure of the study sample, the amount of variance attributable to the locus, and the information content of the marker appear to affect the ability to detect genotype-phenotype relationships using linkage analysis.

Genetic variation in paraoxonase-1 and paraoxonase-2 is associated with variation in plasma lipoproteins in Alberta Hutterites.

In a sample taken from the genetically isolated Alberta Hutterites, we previously found that PON1 variation was associated with variation in plasma lipoprotein traits, including LDL and HDL cholesterol. With the recent cloning of the PON1-related gene PON2, we undertook studies of the association between genetic variation in PON2 and variation in plasma quantitative traits variation in a sample of 745 Alberta Hutterites. We found novel genetic associations between PON2 variation and variation in fasting plasma concentrations of total cholesterol and apolipoprotein AI. We confirmed our previously observed significant associations in this study sample between PON1 genetic variation and variation in plasma apo B-related traits, such as LDL, non-HDL and HDL cholesterol and apo B itself. Furthermore, there was almost complete linkage disequilibrium between PON2 alleles G148 and C311. We found no association between PON2 variation and plasma glucose or insulin. Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in both PON1 and PON2 that affects the amino acid sequence of the respective gene products is associated with significant variation in intermediate traits in plasma lipoprotein metabolism.

Genetic variation in factor VII associated with variation in plasma lipoprotein(a) concentration.

Cross-sectional and prospective studies have shown that individuals with high plasma lipoprotein(a) [Lp(a)] concentrations are at increased risk for coronary heart disease. Size polymorphism of the apolipoprotein(a) [apo(a)] glycoprotein accounts for approximately 35% of the variation in plasma Lp(a) concentrations. However, there is no convincing evidence for associations between plasma Lp(a) and common genetic variation outside APO(a), the gene that encodes apo(a). We tested for association of common genetic variation of candidate genes in lipid metabolism and also of F7 with variation of plasma Lp(a) concentrations in Alberta Hutterites. Variation at codon 353 of F7 has been associated with variation in the plasma factor VII activity (FVIIc), with the 353Q allele associated with lower FVIIc and the 353R allele associated with higher FVIIc. We found significant associations between variation in plasma concentrations of Lp(a) and both apo(a) isoform size and F7 codon 353 genotype (both P < .0001). The effects on plasma Lp(a) concentration of the alleles at codon 353 were additive. The average effects of the F7 353Q and 353R alleles were, respectively, to decrease by 1.71 micrograms/mL and to increase by 0.301 microgram/mL plasma Lp(a) concentration from the sample mean. This suggests that common genomic variation in F7 is associated with variation in plasma Lp(a) concentration.

Health promotion in the Hutterite community and the ethnocentricity of empowerment.

Empowerment, one of the cornerstones of health promotion, has been influenced by the transformative and emancipatory perspectives of the revolutionary educator Paulo Freire and critical social theory. The empowerment process is conceived as one of liberation from oppression, powerlessness, and ignorance, and at its core are notions of grassroots activism and rejection of the status quo. This paper critically examines the challenges faced by health-promotion practitioners and researchers who seek to work in an empowering way with a culturally distinct group, the Hutterites. The Hutterian world-view, which values (a) communalism, (b) respect for hierarchical decision-making, and (c) strict adherence to a traditional code of conduct, values, and beliefs, provides an opportunity to critique the ethnocentricity of the empowerment process.

Genetic and biochemical factors associated with variation in blood pressure in a genetic isolate.

We previously found an association between blood pressure and genetic variation of angiotensinogen in Canadian Hutterites. We hypothesized that variation in other candidate genes would also be associated with variation in blood pressure. We included genotypes of 12 candidate genes, along with clinical features and biochemical variables as covariates in an association analysis. We found that sex and body mass were significantly associated with variation in both systolic and diastolic blood pressures. We found that genotypes of APOB codon 4154 and AGT codon 174 were significantly associated with variation in systolic blood pressure. We found that genotypes of APOB codon 4154, AGT codon 174, and F7 codon 353 were significantly associated with variation in diastolic blood pressure. We found a significant association between age and variation in systolic but not diastolic blood pressure. We found a significant association between plasma apo B concentration and variation in diastolic but not systolic blood pressure. The association of genomic variation with resting blood pressure is consistent with the existence of important structural elements within or proximal to some genes in lipoprotein metabolism, the renin-angiotensin system, and the coagulation cascade. The association between plasma apo B concentration and diastolic blood pressure suggests that these traits may share some determinants.

Restriction isotyping of the premature termination variant of lipoprotein lipase in Alberta Hutterites.

OBJECTIVE: Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. A relatively common LPL variant results from a C --> G transversion in exon 9, which creates a premature termination codon (S447X) and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser-Gly. We wished to determine the functional relevance of this variant. DESIGN AND METHODS: We used Mn/l restriction digestion of amplified genomic DNA to genotype Alberta Hutterites for the S447X variant. We tested for association with biochemical phenotypes. RESULTS: Complete linkage disequilibrium between alleles of an LPL genomic variant in intron 6 and LPL S447X was detected. However, as a single independent variable, LPL S447X genotype was not significantly associated with variation in any dependent biochemical variable in the Hutterites. CONCLUSIONS: Restriction isotyping for S447X permits large-scale screening of individuals to identify linkage relationships between this marker and other DNA variations of LPL and to study associations with clinical phenotypes.

Preventive behaviours in the Hutterite community following a nurse-managed cholesterol screening program.

In this study we examined the effect of a nurse-managed cholesterol screening program on the preventive health behaviours (e.g., diet changes, weight loss, medical surveillance) of 534 Hutterites. Hutterites are the largest single rural ethnic group in Canada and they have been found to be at high risk for heart disease. Eighty-one percent of the participants engaged in at least one preventive behaviour. Ongoing cholesterol surveillance was reported by 34.5% of the participants. Weight loss and dietary fat reduction were reported by 31% and 62% of the respondents, respectively. Seven percent of the respondents began lipid-lowering pharmacologic therapy. Screening cholesterol levels and age were significantly related to all of the outcomes except weight loss. This study provides evidence that community-based screening accompanied by counselling and referral by nurses can positively affect preventive behaviours.

Genetic variation on chromosome 1 associated with variation in body fat distribution in men.

BACKGROUND: Interindividual variation in fat deposition in swine is determined by loci on porcine chromosome 4, which are contained in a region that is syntenic with part of the long arm of human chromosome 1. We hypothesized that genomic variation of chromosome 1q would be associated with variation in the ratio of waist-to-hip circumference in male North American Hutterites, a genetic isolate characterized by significant relatedness and sharing of environmental factors. METHODS AND RESULTS: In 316 male Hutterites, we tested for phenotype-genotype association of two DNA polymorphisms on chromosome 1q and the ratio of waist-to-hip circumference. We included control loci on 10 other chromosomes in the multivariate model. We observed that DNA variation on chromosome 1q was significantly associated with variation in the ratio of waist-to-hip circumference in men (P = .0029). CONCLUSIONS: The association of DNA variation chromosome 1q with the ratio of waist-to-hip circumference in male Hutterites suggests that there are important structural elements in this genomic region that have a functional impact on body fat distribution.

Multiple genetic determinants of variation of plasma lipoproteins in Alberta Hutterites.

We hypothesized that variation of nine candidate genes in lipoprotein metabolism would be associated with variation in fasting plasma lipoprotein variables in 718 Alberta Hutterites, a genetic isolate. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apolipoprotein (apo) B (APOB), paraoxonase (PON), lipoprotein lipase (LPL), VLDL receptor (VLDLR), apo CIII (APOC3), LDL receptor-related protein (LRP), hepatic lipase (HL), LDL receptor (LDLR), and apo E (APOE). Using a multivariate analysis, we found that (1) genotypes of APOB, PON, LPL, LDLR, and APOE were significantly associated with variation of plasma apo B-related traits; (2) genotypes of PON, LPL, and APOC3 were significantly associated with variation in plasma triglycerides; and (3) genotypes of VLDLR, APOC3, LDLR, and APOE were significantly associated with variation in plasma apo AI and HDL cholesterol. Regression analysis showed that between 3.2% and 7.8% of the total variation in plasma lipoproteins was accounted for by variation in the candidate genes tested. The observations demonstrate a modest but significant genetic component of variation in plasma lipoprotein levels that is due to the candidate genes studied in this normolipemic human genetic isolate.

A polymorphism of the paraoxonase gene associated with variation in plasma lipoproteins in a genetic isolate.

The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the paraoxonase (PON) gene that underlies the interindividual variation in plasma PON activity would be associated with variation in fasting plasma lipoprotein variables in this group. In 793 Hutterites, we measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of the protein polymorphism at amino acid residue 192 of PON. We observed that genotypes of PON were significantly associated with variation in plasma concentrations of total, HDL, non-HDL, and LDL cholesterol, total triglycerides, and apolipoprotein (apo) B. Homozygotes for the low-activity variant of PON had significantly lower levels of plasma apoB-related biochemical variables than heterozygotes and homozygotes for the high-activity variant of PON. Homozygotes for the low-activity variant of PON also had significantly lower ratios of total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, and apoB/apoA-I than heterozygotes and homozygotes for the high-activity variant of PON. We found no evidence for a gene-gender interaction for any plasma lipoprotein variable. The PON polymorphism accounted for about 1% of the variation in total cholesterol and related lipoprotein traits in the Hutterites. These observations suggest that PON is a significant genetic determinant of plasma lipoprotein levels.

Femoral arterial sheath removal after PTCA: a cross-Canada survey.

A cross-sectional survey was conducted to examine current Canadian practices in the nursing and medical management of femoral arterial sheath removal (SR) after PTCA (percutaneous transluminal coronary angioplasty). The purposes of the study were to (a) investigate the roles of the nurses and physicians in SR, (b) assess the length of time arterial sheaths are left in place and patients kept on bedrest, and (c) describe the routine medical protocols used for pain and anticoagulation therapy. Of the 35 hospitals that perform PTCA in Canada, 30 responded to the survey (response rate of 86%). Nurses had primary responsibility for SR in 13% of the sites and shared responsibility with physicians for SR in a further 10% of the institutions. When nurses were trained to remove sheaths, they assumed responsibility for the adjunctive steps to establish hemostasis. One third of hospitals removed sheaths in 4 hours or less; approximately 75% of them removed sheaths in 6 hours or less after PTCA. Patients are kept on bedrest for 6 hours or less following hemostasis in half, and 8 hours or less at three-quarters of the hospitals. Post-PTCA and pre-SR anticoagulant monitoring was used in almost half of the sites. Premedication for SR varied from no premedication to combinations of three intravenous medications plus local anaesthetic. Survey results showed that in almost one quarter of the Canadian institutions where PTCA is performed, nurses play a role in SR. Results also showed that there is no uniformity in post-PTCA SR across Canada and that further research is needed to identify the optimum approach to managing this common cardiovascular procedure.

A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate.

BACKGROUND: The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes would be associated with variation in resting blood pressure in this group. We also hypothesized that the association would depend on the sex of the subjects. METHODS AND RESULTS: In 741 Hutterites, we measured blood pressure in quadruplicate and analyzed DNA for genotypes of an insertion/deletion (I/D) polymorphism of ACE and of two protein polymorphisms of AGT, namely, M235T and T174M. We tested for association between variation in systolic and diastolic blood pressures and genotypic class. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure. We also tested for an interaction between the AGT genotype and sex. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure only in men. The AGT codon 174 polymorphism accounted for 3.1% of the total variation in systolic blood pressure in men. CONCLUSIONS: The association of AGT variation with resting blood pressure in men is consistent with the existence of important structural elements within, flanking, or proximal to the AGT gene, whose functional impact might be related to differences in sex.

A comparison of physical and laboratory measures between two Hutterite leute and the rural Saskatchewan population.

This study compares physical, laboratory and anthropometric measurements from each of two groups (leute) of Hutterites (N = 846) with a population of non-Hutterites from rural Saskatchewan (N = 750). Marked interleute differences were observed in the comparative analysis with the non-Hutterite population. Dariusleut males had significantly greater mean diastolic and systolic blood pressures, total cholesterols, LDL cholesterols and Body Mass Indexes (BMI) than non-Hutterites. Compared with non-Hutterite women, the Dariusleut females had significantly greater mean diastolic and systolic blood pressure, HDL cholesterols, BMIs and waist-hip ratios. In contrast, the only significant difference between non-Hutterites and Lehrerleut males was in BMI. Lehrerleut females had significantly greater mean systolic blood pressures, HDL cholesterol levels and BMIs. While the surprising inter-leute differences may be due to subtle variations in lifestyle, the genetic isolation of the groups suggests heredity may offer a more likely explanation for the differences.

A gene-gender interaction affecting plasma lipoproteins in a genetic isolate.

The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation in their apolipoprotein (apo) E and lipoprotein lipase (LPL) genes would be associated with variation in fasting plasma lipoproteins. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apoE and LPL in 803 Hutterites. We observed that apoE and LPL genotypes were significantly associated with variations in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and apoB. When the data were subdivided by sex, apoE genotype was associated with plasma apoB-related traits in men, but LPL genotype was not. In contrast, LPL genotype was associated with plasma apoB-related traits in women, including triglycerides and LDL cholesterol. After accounting for age, body mass index, and colony of origin, the variation in these variables was much more significantly associated with LDL genotype than with apoE genotype in women but not in men. The association of LPL variation with plasma lipoproteins in women suggests that the functional effects of important structural elements within, flanking, or proximal to the LPL gene on chromosome 8p22 may be sex related.

Hypertension and its correlates in the Hutterite community of Alberta.

The purpose of this study was to determine the prevalence of hypertension and its correlates in the Hutterite population of Alberta. A total of 811 subjects from 38 Hutterite colonies participated in the survey. A self- and interviewer-administered questionnaire gathered information about past medical history, lifestyle habits, and family history. Blood pressure, blood cholesterol, 2 hour postprandial blood glucose and height and weight were also measured. The prevalence of diastolic blood pressure > or = 90 mm Hg was approximately twice that reported in other Canadian surveys: 60% and 30% for the males and females respectively. Half of the participants found to be hypertensive were unaware of their condition and of those aware, 76% were uncontrolled. There were significant correlations between diastolic blood pressure and Body Mass Index (BMI), cholesterol, age and glucose. This study supports the need for the development of culturally appropriate health promotion programs related to hypertension in this population.

Evaluation of hypertension screening in the Hutterite population.

The purpose of this study was to examine the impact of a hypertension screening program on Hutterites from Alberta, Canada who were found to have a diastolic blood pressure greater than 90 mm Hg. At approximately 16 months postscreening, 200 subjects completed a self-administered questionnaire requesting information about physician follow-up and pharmacologic and nonpharmacologic therapy. Seventy-four percent of the subjects reported that they had their blood pressure measured at least twice since screening. A third of the respondents reported changes in pharmacologic management. Subjects reported weight loss (36%), and salt and alcohol reduction (64% and 48%, respectively) as nonpharmacologic methods for lowering blood pressure. In terms of physician follow-up and pharmacologic and nonpharmacologic modification, the screening program was effective.