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Biomedical subjects

S B Harris

Publications and source records attributed to S B Harris.

At least 55 records · Page 3Linked to original sources
PubMed1999

Association between AGT T235 variant and microalbuminuria in Canadian Oji-Cree with type 2 diabetes mellitus.

OBJECTIVE: To assess the association between the common variation in the gene encoding angiotensinogen, AGT, and the presence of microalbuminuria in Canadian Oji-Cree with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We compared the frequencies of the AGT promoter and M235T polymorphisms among three subgroups of adult Oji-Cree: 50 subjects who had type 2 diabetes with microalbuminuria, 6 subjects who had type 2 diabetes without albuminuria and 302 non-diabetic, normotensive subjects. RESULTS: We found the AGT T235 allele was present at a significantly higher frequency, and that T235/T235 homozygotes were significantly more prevalent, among the subjects who had type 2 diabetes with microalbuminuria than among the subjects in the other two groups. CONCLUSIONS: The findings suggest that the AGT T235 allele is a determinant of the nephropathy susceptibility related to type 2 diabetes in these aboriginal Canadians.

Adolescent↗
PubMed1999

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.

Adolescent↗
PubMed1999

Association between AGT codon 235 polymorphism and variation in serum concentrations of creatinine and urea in Canadian Oji-Cree.

Finding the genetic determinants of intermediate quantitative traits, such as serum creatinine and urea, might aid in finding the determinants of disease phenotypes, such as renal failure, that are, in part, defined according to threshold values imposed upon such traits. We evaluated the association between common variation in the gene encoding angiotensinogen, AGT, and the serum concentrations of creatinine and urea in non-diabetic Canadian Oji-Cree. We determined genotypes of the AGT codon 235 polymorphism among 502 non-diabetic Oji-Cree. We used multivariate analysis of variance to identify significant determinants of variation in serum concentrations of creatinine and urea and of systolic and diastolic blood pressure. We found significant associations between the AGT codon 235 genotype and serum concentrations of creatinine and urea (p = 0.017 and 0.049, respectively) and systolic blood pressure (p = 0.041). Compared with subjects with the other two genotypes, homozygotes for AGT T235/T235 had significantly lower serum concentrations of creatinine and urea and significantly higher mean systolic blood pressure. The findings suggest that the AGT T235 allele is a determinant of intermediate traits related to renal function in these aboriginal Canadians.

Adolescent↗
PubMed1999

The aetiology of acute rupture of flexor tendon repairs in zones 1 and 2 of the fingers during early mobilization.

Five hundred and eight patients with 840 acute complete flexor tendon injuries in 605 fingers in zones 1 and 2 underwent surgery and postoperative mobilization in a controlled or early active motion (active flexion-active extension) regimen over a period of 7.5 years. Sixty-eight patients with 79 finger flexor divisions who did not complete the rehabilitation programme were excluded. Of the 440 patients with 728 complete tendon divisions in 526 fingers included in the study, 23 patients ruptured 28 tendon repair(s) in 23 fingers, an overall rupture rate of 4%. One hundred and twenty-nine fingers with zone 1 injuries had a rupture rate of 5%. Three hundred and ninety-seven fingers with zone 2 injuries had a rupture rate of 4%. This study analyses the 23 patients with flexor tendon rupture(s) to identify causative factors. In approximately half of these patients, tendon rupture followed acts of stupidity. The implications of this are discussed. There was no significant relationship between tendon rupture and the age or sex of the patients, smoking or delay between injury and tendon repair and there was no particular prevalence of zone 2C level injuries among the fingers in which tendon rupture occurred.

Adolescent↗
PubMed1999

Circulating tumor necrosis factor-alpha concentrations in a native Canadian population with high rates of type 2 diabetes mellitus.

Recent research suggests that tumor necrosis factor-alpha (TNF alpha) may play an important role in obesity-associated insulin resistance and diabetes. We studied the relationship between TNF alpha and the anthropometric and physiological variables associated with insulin resistance and diabetes in an isolated Native Canadian population with very high rates of type 2 diabetes mellitus (DM). A stratified random sample (n = 80) of participants was selected from a population-based survey designed to determine the prevalence of type 2 DM and its associated risk factors. Fasting blood samples for glucose, insulin, triglyceride, leptin, and TNF alpha were collected; a 75-g oral glucose tolerance test was administered, and a second blood sample was drawn after 120 min. Insulin resistance was estimated using the homeostasis assessment (HOMA) model. Systolic and diastolic blood pressure (BP), height, weight, and waist and hip circumferences were determined, and percent body fat was estimated using biological impedance analysis. The relationship between circulating concentrations of TNF alpha and the other variables was assessed using Spearman correlation coefficients, analysis of covariance, and multiple linear regression. The mean TNF alpha concentration was 5.6 pg/mL (SD = 2.18) and ranged from 2.0-12.9 pg/mL, with no difference between men and women (P = 0.67). There were moderate, but statistically significant, correlations between TNF alpha and fasting insulin, HOMA insulin resistance (HOMA IR) waist circumference, fasting triglyceride, and systolic BP (r = 0.23-0.34; all P < 0.05); in all cases, coefficients for females were stronger than those for males. Individuals with normal glucose tolerance had lower log TNF alpha concentrations than those with impaired glucose tolerance or type 2 DM (both P = 0.03, adjusted for age and sex), although differences were not significant after adjustment for HOMA IR (both P > 0.25). Regression analysis indicated that log HOMA IR and log systolic BP were significant independent contributors to variations in log TNF alpha concentration (model r2 = 0.32). We conclude that in this homogeneous Native Canadian population, circulating TNF alpha concentrations are positively correlated with insulin resistance across a spectrum of glucose tolerance. The data suggest a possible role for TNF alpha in the pathophysiology of insulin resistance.

Adolescent↗
PubMed1999

The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.

Mutations in the gene encoding hepatic nuclear factor-1alpha (HNF-1alpha) have been found in patients with maturity-onset diabetes of the young. We identified a new variant in the HNF-1alpha gene, namely G319S, in Ontario Oji-Cree with type 2 diabetes. G319S is within the proline II-rich domain of the trans-activation site of HNF-1alpha and alters a glycine residue that is conserved throughout evolution. S319 was absent from 990 alleles taken from subjects representing six other ethnic groups, suggesting that it is private for Oji-Cree. We found that 1) the S319 allele was significantly more prevalent in diabetic than nondiabetic Oji-Cree (0.209 vs. 0.087; P = 0.000001); 2) S319/S319 homozygotes and S319/G319 heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95% confidence interval, 2.65-6.03) and 1.97 (95% confidence interval, 1.44-2.70) compared with G319/G319 homozygotes; 3) there was a significant difference in the mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319 subjects affected in the fifth, fourth, and third decades of life, respectively. In subjects with type 2 diabetes, we also found significantly lower body mass index and significantly higher post-challenge plasma glucose in S319/S319 and S319/G319 compared with G319/G319 subjects. Finally, among nondiabetic subjects, S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319 homozygotes. The presence of the private HNF-1alpha G319S variant in a large number of Oji-Cree with type 2 diabetes and its strong association with type 2 diabetes susceptibility are unique among human populations. Also, G319S is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose.

Adolescent↗
PubMed1998

Maternal nutritional status, diabetes and risk of macrosomia among Native Canadian women.

Multivariate methods were used to identify risk factors for macrosomia (birth weight > 4000 g) among 741 singleton births to Native Canadian women from Sioux Lookout Zone, Ontario, Canada, in 1990-1993. The average birth weight was 3691 +/- 577 g, and 29.2% of infants weighed more than 4000 g at birth. Macrosomic infants were born at later gestational ages and were more likely to be male. Women delivering macrosomic infants were taller, entered pregnancy with higher body mass indexes (BMI) and gained more weight during pregnancy, but were less likely to smoke cigarettes. They were more likely to have previously delivered a macrosomic infant and to have had gestational diabetes mellitus (GDM). Risk of macrosomia was associated with maternal glycemic status; women with pre-existing diabetes were at greatest risk, followed by those with GDM A2 (fasting glucose > or = 6 mmol/l). Women with GDM A1 (fasting glucose < 6 mmol/l) were not at increased risk for delivering a macrosomic infant, but glucose-tolerant women with high glucose concentrations 1 h after the 50 g challenge were at somewhat increased risk. Maternal glycemic status and maternal nutritional status before and during pregnancy are important determinants of macrosomia in this native population.

Birth Weight↗
PubMed1998

What works? Success stories in Type 2 diabetes mellitus.

The increasing prevalence of Type 2 diabetes mellitus has made diabetes a major public health problem worldwide. Healthcare systems are faced with the major challenge of developing innovative approaches to improving the prevention of diabetes and associated complications, particularly in populations undergoing rapid cultural development. Examples of community-based primary prevention projects in two Native communities in Canada that have high incidences of diabetes are reviewed. These projects are notable for the active participation of the communities, the collaborative relationship that was established between the communities and the researchers, and the way that traditional native culture and beliefs were incorporated into the intervention design. This phenomenon has impacted on the success of the projects and has enhanced their long-term sustainability.

Canada↗
PubMed1998

-6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree.

We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely -6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the -6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT -6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT -6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of -6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT -6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.

Adult↗
PubMed1998

Specific patterns of food consumption and preparation are associated with diabetes and obesity in a Native Canadian community.

We examined the relationship between usual patterns of food intake, fattiness of food preparation and consumption, and diabetes and obesity status in a Native Canadian reserve in northwestern Ontario. Patterns of intake were estimated using a 34-item food frequency instrument. Scales and scores were developed using factor analysis procedures and were tested for reliability using coefficient alpha. Impaired glucose tolerance (IGT) and diabetes status was determined by administering a 75-g glucose tolerance test. A number of the food groups appear to have a protective effect in regard to IGT and diabetes, including vegetables [odds ratio (OR) = 0.41, confidence interval (CI) = 0.18-0.91], breakfast foods (OR = 0.41, CI = 0.18-0. 93) and hot meal foods (OR = 0.29, CI = 0.11-0.78). Most of these foods are relatively high in fiber and low in fat. High consumption of junk foods and the bread and butter group was associated with substantial increases in risk for diabetes (OR = 2.40, CI = 1.13-5. 10; OR = 2.22, CI = 1.22-4.41, respectively). These foods tend to be high in simple sugars, low in fiber and high in fat. More fatty methods of food preparation are also associated with increased risk for diabetes in this population (OR = 2.58, CI = 1.11-6.02). This information has been incorporated into an ongoing community-based diabetes prevention program in the community.

Adolescent↗
PubMed1998

Genetic variation in paraoxonase-2 is associated with variation in plasma lipoproteins in Canadian Oji-Cree.

We report studies of the association between genetic variation in PON2 and variation in plasma quantitative traits in a sample of 334 non-diabetic Oji-Cree. We detected associations between PON2 variation in codon 148 (Ala --> Gly) and variation in fasting plasma concentrations of total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. In particular, homozygotes for a PON2 allele that encoded A148 had significantly higher plasma total, LDL cholesterol and apo B than subjects having the other two genotypes (p < 0.01). Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in PON2 is associated with significant variation of intermediate traits in plasma lipoprotein metabolism.

Adult↗
PubMed1998

G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji-Cree.

The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure. There is alternative splicing of exon 9 of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) associated with a C-->T change at nucleotide 825, which activates a cryptic splice site. The 825T allele results in a gene product that is 41 amino acids smaller than the wild-type gene product. G protein heterotrimers containing the shorter variant are more reactive than those containing the wild type, and the 825T allele appears to be associated with essential hypertension. To evaluate whether this variant is associated with hypertension or blood pressure in other human samples, we genotyped 447 young adult Oji-Cree for the GNB3 C825T variation. We found that the frequency of the GNB3 825T allele was 0.501 in the Oji-Cree, which is considerably higher than the frequency observed in whites. Furthermore, genetic variation of the GNB3 nucleotide 825 was significantly associated with variation in systolic pressure but not diastolic pressure. Specifically, subjects with the 825T/T genotype had significantly lower systolic pressure than subjects with the 825C/T and 825C/C genotypes; the association was independent of sex. Furthermore, the 825T allele frequency tended to be higher in subjects who took antihypertensive medications than in subjects who did not (0.571 versus 0.496; P=NS), although this young sample had relatively few subjects with hypertension. The findings support an association of variation in this gene with variation in blood pressure.

Adolescent↗
PubMed1998

Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians.

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Canadian Oji-Cree. One of these genes encodes the skeletal muscle regulatory G subunit of the glycogen-associated form of protein phosphatase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymorphism in a messenger ribonucleic acid-stabilizing AU(AT)-rich element within the 3'-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 3'-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or impaired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h postprandial plasma glucose than subjects with the other genotypes. There was no association of the PPPIR3 genotype either with the presence of type 2 diabetes or IGT or with other quantitative traits in this sample. These findings suggest that common PPPIR3 3'-UTR variation that potentially affects messenger ribonucleic acid stability is associated with variation in glycemia in Oji-Cree subjects with type 2 diabetes.

3' Untranslated Regions↗