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Biomedical subjects

C L Hanis

Publications and source records attributed to C L Hanis.

At least 19 recordsLinked to original sources

Physical activity does not mitigate G-protein-related genetic risk for obesity in individuals of African descent.

The G-protein beta3 subunit 825 TT genotype has been associated with obesity and hypertension. We examined the interaction between the G-protein TT genotype, physical activity and body mass index (BMI) in a cross-sectional study of African immigrants and African Americans. The genotype frequencies were 6.3% CC, 37.7% CT, and 56% TT. After adjusting for potential confounders, BMI was found to be significantly higher in the sedentary than in the physically active participants (p=0.045). There was no statistically significant effect for genotype (p=0.215) or the interaction between genotype and the level of physical activity (p=0.219). However, the individuals with the CC or CT genotype who were physically active had substantially lower BMIs (M+/-SE) (i.e., 25.74+/-2.02) than any of the other groups: sedentary CC + CT (30.58+/-1.03), sedentary TT (30.65+/-1.00) or active TT (29.43+/-1.65). Because of the low statistical power of this study, further research is needed to confirm these findings and to explore potential gene-environment/lifestyle interactions.

Adult↗

Genetic bottlenecks, perceived racism, and hypertension risk among African Americans and first-generation African immigrants.

The complexity of factors influencing the development of hypertension (HTN) in African Americans has given rise to theories suggesting that genetic changes occurred due to selection pressures/genetic bottleneck effects (ie, constriction of existing genetic variability) over the course of the slave trade. Ninety-nine US-born and 86 African-born health professionals were compared in a cross-sectional survey examining genetic and psychosocial predictors of HTN. We examined the distributions of three genetic loci (G-protein, AGT-235, and ACE I/D) that have been associated with increased HTN risk. There were no significant differences between US-born African Americans and African-born immigrants in the studied genetic loci or biological variables (eg, plasma renin and angiotensin converting enzyme activity), except that the AGT-235 homozygous T genotype was somewhat more frequent among African-born participants than US-born African Americans. Only age, body mass index, and birthplace consistently demonstrated associations with HTN status. Thus, there was no evidence of a genetic bottleneck in the loci studied, ie, that US-born African Americans have different genotype distributions that increase their risk for HTN. In fact, some of the genotypic distributions evidenced lower frequencies of HTN-related alleles among US-born African Americans, providing evidence of European admixture. The consistent finding that birthplace (ie, US vs Africa) was associated with HTN, even though it was not always significant, suggests potential and unmeasured cultural, lifestyle, and environmental differences between African immigrants and US-born African Americans that are protective against HTN.

Adult↗

Calpains play a role in insulin secretion and action.

Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action.

Adipocytes↗

The Starr County Diabetes Education Study: development of the Spanish-language diabetes knowledge questionnaire.

OBJECTIVE: This study reports the psychometric properties of the 24-item version of the Diabetes Knowledge Questionnaire (DKQ). RESEARCH DESIGN AND METHODS: The original 60-item DKQ was administered to 502 adult Mexican-Americans with type 2 diabetes who are part of the Starr County Diabetes Education Study. The sample was composed of 252 participants and 250 support partners. The subjects were randomly assigned to the educational and social support intervention (n = 250) or to the wait-listed control group (n = 252). A shortened 24-item version of the DKQ was derived from the original instrument after data collection was completed. Reliability was assessed by means of Cronbach's coefficient alpha. To determine validity, differentiation between the experimental and control groups was conducted at baseline and after the educational portion of the intervention. RESULTS: The 24-item version of the DKQ (DKQ-24) attained a reliability coefficient of 0.78, indicating internal consistency, and showed sensitivity to the intervention, suggesting construct validation. CONCLUSIONS: The DKQ-24 is a reliable and valid measure of diabetes-related knowledge that is relatively easy to administer to either English or Spanish speakers.

Adult↗

Prevalence and determinants of type 2 diabetes among Filipino-Americans in the Houston, Texas metropolitan statistical area.

OBJECTIVE: The few available studies suggest that Filipino-Americans have an increased risk for developing type 2 diabetes. The purpose of this study was to determine the prevalence of previously diagnosed type 2 diabetes and its major risk factors among Filipino-Americans. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted in the Houston, Texas, metropolitan statistical area between September 1998 and March 2000. The convenience sample included 831 Filipino-American participants aged 20-74 years. The major risk factors assessed were age, sex, family history of diabetes, socioeconomic status, obesity (BMI >30), physical inactivity, acculturation, region of birth and, in women, history of gestational diabetes and delivery of a baby weighing > 9 lb. RESULTS: Overall prevalence was estimated to be 16.1% (95% CI 13.5-18.7). Multivariate logistic regression analyses identified independent risk factors: increasing age from ages 35-44 years (odds ratio [OR] 5.6, 95% CI 1.5-20.5) to 65-74 years (34.2, 7.2-163.0); male sex (1.8, 1.1-32.1); family history of diabetes (4.7, 2.6-8.5); obesity (3.6, 1.4-9.0); region of birth, Mindanao (3.2, 1.3-7.7); and, among women, gestational diabetes (21.7, 6.7-69.7) and low income (5.3, 1.4-20.2). CONCLUSIONS: The study observed a high prevalence of type 2 diabetes and supports earlier studies suggesting that Filipinos are at higher risk for type 2 diabetes than the U.S. non-Hispanic white population.

Adult↗

Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project.

BACKGROUND: The role of physical activity (PA) in reducing the risk of all-cause mortality or reinfarction after a first myocardial infarction (MI) remains unresolved, particularly for minority populations. The association between change in level of PA and risk of death or reinfarction was studied in 406 Mexican American and non-Hispanic white women and men who survived a first MI. METHODS AND RESULTS: MI patients were interviewed at baseline and annually thereafter about PA, medical history, and risk factors of coronary heart disease. Change in level of PA after the index MI was categorized as (1) sedentary, no change (referent group), (2) decreased activity, (3) increased activity, and (4) active, no change. Over a 7-year period, the relative risk (95% CI) of death was as follows: 0.21 (0.10 to 0.44) for the active, no change group; 0.11 (0.03 to 0.46) for the increased activity group; and 0.49 (0.26 to 0.90) for the decreased activity group. The relative risk of reinfarction was as follows: 0.40 (0.24 to 0.66) for the active, no change group; 0.22 (0.09 to 0.50) for the increased activity group; and 0.93 (0.59 to 1.42) for the decreased activity group. CONCLUSIONS: These findings are consistent with a beneficial role of PA for Mexican American and non-Hispanic white women and men who survive a first MI and have practical implications for the management of MI survivors.

Adult↗

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Adult↗

Sequence variation within the neuropeptide Y gene and obesity in Mexican Americans.

OBJECTIVE: Recently, we reported evidence for linkage between neuropeptide Y (NPY) and both obesity and several obesity-related quantitative measures in a sample of Mexican Americans from Starr County, Texas. The purpose of this study was to investigate putative variation within the coding and promoter regions of NPY. RESEARCH METHODS AND PROCEDURES: Five young, obese individuals (body mass index [BMI] 33 to 45 kg/m2, age 14 to 30 years); five adult, lean individuals (BMI 20 to 26 kg/m2, age 39 to 65 years); and five sibling pairs sharing no alleles that were identical by descent at a marker locus proximal to NPY were selected for fluorescence-based sequencing of approximately 1100 base pairs (bp) immediately 5' from the start site and all four exons of NPY. We identified a total of eight variant sites, including a 2-bp insertion/deletion (I/D) within a putative negative regulatory region (-880I/D) and a 17-bp deletion at the exon 1/intron 1 junction (69I/D). The -880I/D and 69I/D variants were typed in a separate random sample of Mexican Americans (N = 914) from Starr County, Texas. RESULTS: Analyses of variance resulted in a significant association between -880I/D and waist-to-hip ratio (p = 0.041) in the entire sample and between -880I/D and BMI (p = 0.031), abdominal circumference (p = 0.044), and waist-to-hip ratio (p = 0.041) in a non-obese subsample (BMI < 30 kg/m2, n = 594). The 69I/D variant was observed in only one pedigree and does not appear to segregate with obesity within this pedigree. DISCUSSION: This study reports newly identified common human sequence variation within the regulatory and coding sequence of NPY. Several variants were observed, and of those tested, the -880I/D promoter region variant may influence body fat patterning in non-obese individuals but does not appear to play a major role in the etiology of common forms of obesity in this population.

Adolescent↗

Linkage analysis of candidate obesity genes among the Mexican-American population of Starr County, Texas.

Recent advances in the molecular basis of body fat regulation have identified several genes in which genetic variation may influence obesity and related measures in human populations. Genes that have been shown to have a regulatory function in the control of body fat utilization, eating behavior, and/or metabolic rate in rodent models of obesity include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPY Y1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), and uncoupling protein 1 (UCP1). We have typed microsatellite markers located within or near these seven candidate obesity genes in 302 non-diabetic individuals from 59 Mexican-American families from Starr County, Texas. Sib pair linkage analysis was used to examine linkage between these genes and obesity status (obese siblings only; n = 170 pairs) and several obesity-related quantitative variables (all siblings; n = 545 total sibling pairs). Significant linkage (P = 0.042) was found between obesity and NPY within the obese sibling pairs. No other candidate gene was linked to obesity status in this subsample. Consistent with the obese sib pair linkage results, NPY showed evidence of linkage to body weight (P = 0.020), abdominal circumference (P = 0.031), hip circumference (P = 0.012), diastolic blood pressure (P = 0.005), and a composite measure of body mass and size (P = 0.048) in the entire sibling sample. Other significant linkages observed were between LEP and waist/hip ratio (P = 0.010), total cholesterol (P = 0.030), and HDL cholesterol (P = 0.026) and between LEPR and fasting blood glucose (P = 0.018) and diastolic blood pressure (P = 0.003). These results support further investigation of NPY, LEP, and LEPR to identify genetic variation that may influence obesity status, glucose and lipid metabolism, and blood pressure in Mexican Americans.

Adult↗

Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans.

Complex disorders such as diabetes, cardiovascular disease, asthma, hypertension and psychiatric illnesses account for a large and disproportionate share of health care costs, but remain poorly characterized with respect to aetiology. The transmission of such disorders is complex, reflecting the actions and interactions of multiple genetic and environmental factors. Genetic analyses that allow for the simultaneous consideration of susceptibility from multiple regions may improve the ability to map genes for complex disorders, but such analyses are currently computationally intensive and narrowly focused. We describe here an approach to assessing the evidence for statistical interactions between unlinked regions that allows multipoint allele-sharing analysis to take the evidence for linkage at one region into account in assessing the evidence for linkage over the rest of the genome. Using this method, we show that the interaction of genes on chromosomes 2 (NIDDM1) and 15 (near CYP19) makes a contribution to susceptibility to type 2 diabetes in Mexican Americans from Starr County, Texas.

Chromosomes, Human, Pair 15↗

D4 dopamine receptor gene exon III polymorphism and obesity risk.

Many genes have been identified that may play a role in increasing individual susceptibility to obesity. Reduced dopamine function appears to play a role in dysfunctional eating patterns and may predispose some individuals to obesity. The long version of the D4 dopamine receptor gene (D4DR) has been shown to alter receptor function and reduce intracellular response to dopamine. It also has been associated with novelty-seeking-related personality traits that are found with greater frequency in obese individuals. We examined the association between the long alleles of the D4DR and obesity in a sample of 115 obese patients participating in a weight management program. No direct relationship was found between the D4DR and body mass or novelty-seeking-related personality traits. We constructed four models of increased obesity risk that included combinations of traditional risk factors (i.e., long-term history of obesity, parental obesity, a body mass index > 40) and elevations on the novelty-seeking-related scales of the Karolinska Scales of Personality. There was a significant increase in the frequency of the D4DR long alleles in individuals defined as high risk using the combination of novelty-seeking-related personality traits, severe obesity (i.e., BMI > 40), and any other traditional risk factor, but not with the traditional risk factors alone. These preliminary data suggest a potential role for the D4DR gene in increasing obesity susceptibility.

Adult↗

Evaluation of the factor structure and psychometric characteristics of the General Well-Being Schedule (GWB) with Mexican American women.

The General Well-Being Schedule (GWB) is a brief, reliable, and valid measure of subjective well-being that is widely used in research as an indicator of psychological health and dysfunction. The GWB is hypothesized to have six subscales or dimensions (anxiety, depression, positive well-being, self-control, vitality, and general health), but previous research has not yielded a consistent factor structure. Little attention has been paid to the reliability and validity of the GWB with Mexican-Americans, the fastest growing minority group in the U.S. The purpose of this study was to evaluate the reliability and validity of the GWB schedule with Mexican-American women involved in a community-based weight-loss study. Factor analysis indicated a four-factor solution. The GWB and the resulting factors demonstrated acceptable reliability and discriminability.

Adolescent↗

Summary measures of the insulin resistance syndrome are adverse among Mexican-American versus non-Hispanic white children: the Corpus Christi Child Heart Study.

BACKGROUND: Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population. METHODS AND RESULTS: Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus -0.97, P<.0001; girls, 0.52 versus -0.30, P<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus -0.72, P<.0001; girls, 0.35 versus -0.04, P=.056). CONCLUSIONS: Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.

Blood Pressure↗

Cardiovascular risk factors in Mexican-American and non-Hispanic white children: The Corpus Christi Child Heart Study.

BACKGROUND: Information concerning differences in cardiovascular disease risk factors between Mexican-American and non-Hispanic white children is limited. We conducted a study to determine if there were ethnic differences in cardiovascular disease risk factors in children and whether such differences were explained by differences in body mass index. METHODS AND RESULTS: Fasting glucose, insulin, and blood lipid concentrations, blood pressure, weight, and height were measured in a cross-sectional survey among 403 third-grade children in Corpus Christi, Tex. We found significantly higher fasting insulin and glucose concentrations among Mexican-American than among non-Hispanic white children. Mexican-American boys had slightly lower levels of HDL cholesterol and higher systolic blood pressure than non-Hispanic white boys. Ethnic differences in insulin and glucose were not explained by body mass index. CONCLUSIONS: These results provide preliminary evidence that ethnic differences in insulin, glucose, body mass index, and other risk factors occur as early as age 8 to 10 years. Additional research is warranted on differences in risk factors in Mexican-American and non-Hispanic white children and the potential importance of insulin in influencing the natural history of these characteristics.

Blood Glucose↗

Searching for NIDDM susceptibility genes: studies of genes with triplet repeats expressed in skeletal muscle.

The expansion of trinucleotide repeats has been associated with late-onset neurodegenerative disorders. Although the genes harbouring the triplet expansions may be widely expressed, the pathological expression of these diseases is restricted to specific tissues. Non-insulin-dependent diabetes mellitus (NIDDM) shares several features with diseases resulting from such dynamic mutations including late-onset and specific but limited sites of tissue pathology-muscle, fat, liver and insulin-secreting pancreatic beta cells. In order to examine the contribution of genes containing polymorphic CAG/CTG repeats to the development of NIDDM, we screened an adult human skeletal muscle cDNA library for expressed sequences containing tandem repeats of CAG and/ or CTG. Ten different loci with polymorphic CAG/ CTG repeats were identified, of which seven had a heterozygosity greater than 0.20. There was no evidence for linkage between these seven loci and NIDDM in a group of affected Mexican-American sib pairs. Nor was there a significant difference in the distribution of alleles between Caucasian patients with NIDDM and normal healthy control subjects or evidence for repeat expansion in diabetic subjects. Thus, muscle genes with polymorphic CAG/CTG repeats do not appear to play a significant role in the development of NIDDM.

Adult↗

OB gene not linked to human obesity in Mexican American affected sib pairs from Starr County, Texas.

Obesity is a highly prevalent disease, which is associated with a number of chronic conditions and, as such, represents a major public health burden. Numerous studies indicate that there is a genetic component contributing to interindividual variability in obesity. The discovery of the ob gene in mice, mutations in which produce extreme obesity and non-insulin-dependent diabetes mellitus (NIDDM), provides a prime candidate gene for human obesity. We investigated linkage between the human OB gene and obesity in a sample of Mexican Americans from Starr County, Texas. Markers D7S635 and D7S1875, estimated to lie within a region approximately 290 to 400 kb proximal to the OB gene, were used to genotype 177 obese individuals distributed in 64 sibships. Obesity was defined as a body mass index (BMI) above 30 kg/m2. Linkage analyses for affected sibling pairs provided no evidence for linkage in this sample. In addition, differences between siblings for weight, BMI, systolic and diastolic blood pressure, percent body fat, waist-to-hip ratio, and blood lipid measures were not significantly related to number of alleles shared identical by state (IBS) for either of the two markers. While the OB gene may be involved in the metabolic sequences leading to obesity, the present linkage results do not support the existence of common genetic variation at or near the OB locus that increases risk for human obesity.

Adult↗