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A J Hanley

Publications and source records attributed to A J Hanley.

54 records · Page 3Linked to original sources
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↗
PubMed1998

Absence of association between genetic variation of the beta 3-adrenergic receptor and metabolic phenotypes in Oji-Cree.

OBJECTIVE: To assess the association between the common missense variant, Y64R, in the gene encoding the beta 3-adrenergic receptor, ADRB3, and intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree. RESEARCH DESIGN AND METHODS: We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We tested for associations with multivariate analysis of variance. RESULTS: We found the ADRB3 R64 allele frequency to be 0.40 in this population, which is the highest yet observed in a human population. Furthermore, 15% of subjects were R64/R64 homozygotes, compared with a virtual absence of homozygotes in European study samples. However, we found no statistically significant associations of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity, or with intermediate quantitative biochemical traits related to NIDDM. CONCLUSIONS: Despite the very high frequency of the ADRB3 R64 allele in this sample of aboriginal people, it was not associated with any metabolic phenotype. This suggests that the ADRB3 R64 allele is probably not a major determinant of obesity or NIDDM in these aboriginal Canadians.

Adipose Tissue↗
PubMed1997

Low dietary fiber and high protein intakes associated with newly diagnosed diabetes in a remote aboriginal community.

The high prevalence of diabetes mellitus in North American aboriginal populations may be due to recent changes in lifestyle, including the adoption of a high-fat, low-fiber diet. To determine whether fat or fiber intakes were associated with new cases of diabetes, we studied 72% (728/1018) of residents aged > 9 y from a remote aboriginal community in northern Ontario using the 75-g oral-glucose-tolerance test and 24-h dietary recall. The mean fat intake of this population (36% of energy) was typical for North America, but fiber intake (1.2 g/MJ) was very low. Logistic-regression analysis, adjusted for age, sex, and body mass index, showed that a 1-SD increase in fiber intake reduced the risk of having diabetes by 39% (P = 0.026) whereas the same increase in protein intake increased the risk by 38% (P = 0.027). There was no significant effect of energy, fat, starch, or simple sugars. These data support Trowell's original dietary-fiber hypothesis that "... dietary fiber depleted starchy foods are conducive to the development of diabetes mellitus in susceptible human genotypes."

Adolescent↗
PubMed1997

Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins.

We hypothesized that common genomic variation that affected the expression and/or function of the products of the APOC3, APOE, FABP2, and PON1 genes would be associated with variation in biochemical phenotypes in a previously unstudied human sample. We determined genotypes of functional genomic variants of APOC3, APOE, FABP2, and PON1 in 509 adult aboriginal Canadians from an isolated community in Northern Ontario. We tested for genotype associations with plasma lipoprotein traits. We found that (1) common variation at nucleotide -455 of the APOC3 promoter was associated with variation in plasma triglycerides (P = .006) and (2) common variation of APOE determining plasma isoforms of apo E was associated with variation in plasma apo B (P = .009). Analysis of subjects classed by APOC3 markers showed that homozygosity for presence of a C at nucleotide -455 and a T at nucleotide -482 was associated with significantly increased plasma triglycerides in both men and women. Furthermore, this allele was approximately twice as frequent in subjects within the highest quartile of plasma triglycerides as in subjects within the lowest quartile. Since the DNA variation detected by the APOC3 markers affects in vitro expression of the gene product, it is possible that the marker itself caused the associations. However, the associations could also have resulted from linkage disequilibrium with other functional variants in APOC3 or the closely linked APOA1 and/or APOA4 genes.

Adolescent↗
PubMed1997

Common genomic variants associated with variation in plasma lipoproteins in young aboriginal Canadians.

We hypothesized that common genomic variants would be associated with variation in lipoprotein phenotypes in young subjects. We determined genotypes of FABP2, PON, APOC3, and APOE in 188 aboriginal Canadians, aged 9 to 17 years. We found that 13 of 32 possible genotype-phenotype associations were significant: (1) the FABP2 codon 54 genotype was associated with variation in plasma triglycerides (P = .045); (2) the PON codon 192 genotype was associated with variation in plasma total and LDL cholesterol and apoB (P = .0099, P = .0088, and P = .016, respectively); (3) the APOC3 insulin-response-element genotype was associated with variation in plasma triglycerides, HDL cholesterol, apoA-I, the total cholesterol to HDL cholesterol ratio, and the apoB to apoA-I ratio (P = .0014, P = .0069, P = .045, P = .0021, and P = .0081, respectively); and (4) the APOE restriction isotype was associated with variation in plasma LDL cholesterol, apoB, the total cholesterol to HDL cholesterol ratio, and the apoB to apoA-I ratio (P = .025, P = .034, P = .045, and P = .047, respectively). The average young age and relative absence of age-dependent secondary environmental factors could have eased the identification of small genetic effects on lipoprotein phenotypes in this study sample.

Adolescent↗
PubMed1997

Angiotensinogen gene variation associated with variation in blood pressure in aboriginal Canadians.

We measured blood pressure and related clinical phenotypes in 497 adult native Canadians from an isolated community in Northern Ontario. We analyzed their DNA for genotypes of angiotensinogen. We found that the frequency of the T235 variant of the angiotensinogen gene was 0.89 in this sample. This variant was associated with a significantly increased systolic pressure but not diastolic pressure. We also found that sex and body mass were each highly significantly associated with variation in both systolic and diastolic pressures. We found a significant association between age and variation in systolic pressure but not diastolic pressure. We also found a highly significant association between plasma apolipoprotein B concentration and variation in diastolic pressure but not systolic pressure. The high frequency of the angiotensinogen T235 variant suggests that subjects in this young, essentially normotensive population might be predisposed to hypertension, which may become more apparent in the presence of secondary factors.

Adult↗
PubMed1997

Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus.

Defining the genetic determinants of NIDDM requires evidence from several complementary approaches, including both linkage and association analyses using both discrete phenotypes and intermediate quantitative traits. We tested for association between common genomic variation in three genes that map to chromosome 7q21-q22 and quantitative traits related to NIDDM in a sample of Oji-Cree. We found that a common genomic variation in codon 148 (alanine or glycine) of the paraoxonase-2 gene (PON2) demonstrated a significant association with a variation in fasting plasma glucose (P < 0.0001). Furthermore, we found a significant association between a variation in fasting plasma glucose and the interaction term comprised of a PON2 codon 148 genetic variation and the presence of noninsulin-dependent diabetes mellitus (NIDDM; P < 0.0001). We then analyzed subjects according to PON2 genotype and NIDDM status. In subjects with NIDDM, the PON2 codon 148 G/G homozygotes had significantly higher mean fasting plasma glucose than subjects with the other two genotypes (P < 0.0001). However, in non-NIDDM subjects, there was no difference in mean fasting plasma glucose among any of the genotypes. There was no association of the PON2 genotype with NIDDM itself, with impaired glucose tolerance, or with other quantitative traits related to NIDDM in this sample. These findings suggest that 1) the PON2 G148 gene variant worsens glycemia in subjects with NIDDM; 2) defining the physiological role of the PON2 gene product would be worthwhile; and 3) genetic factors can modify the severity of clinical phenotypes in subjects with NIDDM.

Adolescent↗
PubMed1997

Serum immunoreactive leptin concentrations in a Canadian aboriginal population with high rates of NIDDM.

OBJECTIVE: To better understand the relationship between leptin and the anthropometric and physiological variables associated with diabetes, we measured this protein in an isolated Canadian aboriginal population with very high rates of NIDDM. RESEARCH DESIGN AND METHODS: There were 728 individuals aged 10-79 years who participated in a population-based survey to determine the prevalence of NIDDM and its associated risk factors. Fasting blood samples for glucose, insulin, triglyceride, and leptin were collected; a 75-g oral glucose tolerance test was administered and a second blood sample drawn after 120 min. Height, weight, and waist and hip circumference were determined, and percent body fat was estimated using biological impedance analysis. Fitness level was assessed in a subsample of individuals using a validated submaximal step test. The relationship between serum leptin and the other variables was assessed using Spearman's correlation coefficients and multiple linear regression. RESULTS: Serum leptin concentration was strongly correlated with adiposity, and levels were substantially higher in female subjects in all age-groups. For male subjects, percent body fat, fasting insulin level, and waist circumference were significant independent predictors of log serum leptin concentration in a multiple linear regression model (R2 = 0.582). For female subjects, these variables plus glucose tolerance status were included in the final model (R2 = 0.633). Fitness level, when included with the main effects of the above models, was a significant predictor for male subjects only. CONCLUSIONS: In an isolated aboriginal community with high rates of diabetes, we found significant independent relationships between leptin and percent body fat and between leptin and fasting insulin. As documented in other populations, the higher leptin concentration among female subjects may reflect differential leptin production from different adipose tissue beds, or leptin resistance. Independent relationships also existed among leptin and glucose tolerance status in female subjects and fitness level in male subjects.

Adolescent↗
PubMed1996

Body image concepts differ by age and sex in an Ojibway-Cree community in Canada.

Community-based studies of body image concepts can be useful for developing health interventions to prevent obesity-related diseases such as diabetes and cardiovascular disease in specific populations. First Nations peoples, in particular, face increased obesity-related health problems as a result of acculturative changes in diet and activity. This study examined body shape perception in an Ojibway-Cree community in Northern Ontario, Canada. A set of figure outline drawings ranging from very thin to very obese were used to examine perceived body shape, body shape satisfaction and ideals of healthiness across sex and age groups. Overall, only 16% of the population were satisfied with their current body shape. People with a higher body mass index (BMI) were less satisfied with their bodies and thought they were less healthy than people with a lower BMI. While females had a significantly greater BMI than males, males and females did not differ significantly in perception of current body shape. On the other hand, females desired relatively smaller body shapes than males (P < 0.05). Older people chose significantly larger healthy body shapes than did younger people (P < 0.05). Differences between our results and those reported for Anglo populations indicate that while both groups prefer body shapes smaller than those they have currently, the Ojibway-Cree tend to prefer relatively larger body shapes. Knowledge of age and sex-related patterns of body image concepts in communities can assist in the design of obesity-reducing interventions targeting specific groups.

Adolescent↗
PubMed1996

Genetic variation of intestinal fatty acid-binding protein associated with variation in body mass in aboriginal Canadians.

We hypothesized that genomic variation affecting the primary amino acid sequence of the intestinal fatty acid-binding protein would be related to variation in body mass index and associated clinical phenotypes in aboriginal Canadians. We studied 507 adult native Canadians from an isolated community in Northern Ontario. We found that the frequency of the T54 variant of the intestinal fatty acid-binding protein gene was 0.14 in this sample. The presence of this variant was associated with significant increases in body mass index, percent body fat, and fasting plasma triglyceride concentration (P = 0.012, 0.019, and 0.012, respectively). However, the variant was not associated with the presence of diabetes mellitus. These findings suggest that the T54 variant of the intestinal fatty acid-binding protein is associated with differences in fat metabolism in this aboriginal population.

Adult↗
PubMed1995

Cancer mortality among Chinese migrants: a review.

BACKGROUND: Epidemiological studies of cancer among migrant groups are beneficial in that they can provide insight into genetic and environmental factors in disease aetiology. Seven studies in the epidemiological literature have examined cancer mortality in migrants from China; methodological features and findings, which display remarkable consistencies between studies, are reviewed here. METHODS: Papers were included that compare site-specific cancer mortality patterns in first and second generation migrants to the experience in the host regions using vital statistics and census data. Rates had to be standardized either indirectly (using age-specific rates from the host regions) or directly (using a standard age structure) and standardized mortality ratios (SMR) or rate ratios (RR) were calculated. RESULTS: Migrant males had overall mortality from cancer that was often in significant excess compared to the host experience; results for females (for overall cancer) were equivocal. Both sexes had large and significant excess mortality from nasopharyngeal and liver cancer; SMR and RR were also consistently elevated for cancers of the stomach and oesophagus. There was notable attenuation in the high risk at these four sites in the second generation. All studies reported pronounced and significant reduced risk for prostatic cancer and female breast cancer, with little or no increase in mortality in the second generation. The SMR and RR also tended to be below unity for brain, bladder and kidney cancer. CONCLUSIONS: The results of this review indicate that cancer risk at several sites among Chinese migrants appears to be in transition, and that these findings are consistent across studies.

Canada↗
PubMed1993

Use of surnames to identify individuals of Chinese ancestry.

The objectives of this study were to develop and test surname lists for identifying Chinese ancestry. The Ontario all-cause mortality database for the period 1982-1989 was randomly split into source and test data sets. Frequencies by birthplace were compiled for each surname in the source data set, by sex, and the surnames were weighted based on their positive likelihood ratios. Lists of Chinese surnames were then assembled based on varying cutoff levels, and screening performance indicators for each list were calculated, including sensitivity, specificity, positive and negative predictive values, post-test odds, positive likelihood ratio, and yield. The internally generated lists were evaluated in the test data set. Results indicated that surnames have a good potential to identify individuals of Chinese origin. In the source data set, at a cutoff level of 100 for males (217 surnames) and females (210 surnames), both sensitivity and the positive predictive value of the surname lists for males and females were very high, above 80%, and the positive likelihood ratio was above 600. In the test data set and using the same surname lists, the sensitivity, positive predictive value, and positive likelihood ratio remained at a high level: 73%, 81%, and 603, respectively, for males; and 73%, 84%, and 772, respectively, for females. Various scenarios and their methodological implications are discussed.

China↗