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C L Hanis

Publications and source records attributed to C L Hanis.

At least 37 records · Page 2Linked to original sources
PubMed1996

A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Chromosomes, Human, Pair 2↗
PubMed1996

An approach for identifying simple sequence repeat DNA polymorphisms near cloned cDNAs and genes. Linkage studies of the islet amyloid polypeptide/amylin and liver glycogen synthase genes and NIDDM.

Genetic factors contribute to the development of NIDDM, and genes involved in regulating pancreatic beta-cell function and insulin's effects on glucose metabolism are good candidates for being NIDDM susceptibility loci. However, testing candidate genes for linkage to NIDDM depends on the identification of highly informative DNA polymorphisms in or near the candidate locus. Here we describe an approach for identifying highly polymorphic markers near candidate genes that utilizes the emerging physical map of the human genome. A sequence-tagged site from the candidate gene is used to screen the Centre d'Etude du Polymorphisme Humain megabase-insert yeast artificial chromosome library, which contains information on the physical localization of >3,000 genetically mapped simple sequence repeat DNA polymorphisms. Thus, identification of a yeast artificial chromosome containing the candidate locus will in many instances also identify a physically linked simple sequence repeat DNA polymorphism that can be used as a marker for the candidate gene in linkage studies. We have used this approach to identify a marker for the islet amyloid polypeptide gene on chromosome 12. The physical mapping of this gene to a yeast artificial chromosome showed that it was in the same yeast artificial chromosome as the gene encoding liver glycogen synthase, another possible NIDDM susceptibility gene. Affected sib pair studies using a simple sequence repeat DNA polymorphism physically linked to the islet amyloid polypeptide and liver glycogen synthase genes showed no evidence for linkage with NIDDM, indicating that they are not major genes contributing to NIDDM susceptibility.

Amyloid↗
PubMed1996

The GENNID Study. A resource for mapping the genes that cause NIDDM.

OBJECTIVE: To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS: Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, are being collected by the eight Harold Rifkin Family Acquisition Centers. Detailed family and medical histories are obtained from all participants. Family members with diabetes have fasting blood samples drawn, while nondiabetic family members have an oral glucose tolerance test and, when possible, insulin sensitivity and insulin secretion measurements by frequently sampled intravenous glucose tolerance testing or euglycemic insulin clamp. Lymphoblastoid cell lines are established for all participants. RESULTS: Over 1,400 individuals from approximately 220 families have been studied since the start of the GENNID (Genetics of NIDDM) program in July 1993. The goal is that by July 1997, data from 300 non-Hispanic white families, > 100 Hispanic families, > 100 African-American families, and 15 Japanese-American families will have been collected. CONCLUSIONS: The identification of the genes responsible for NIDDM may now be achievable, but only if sound phenotypic data are linked to genetic material from a large number of well-described multiplex families. The GENNID project of the American Diabetes Association is creating a comprehensive resource that will expedite the identification of the genetic basis of NIDDM.

Black or African American↗
PubMed1996

Hypertension among Mexican Americans in Starr County, Texas.

THE MEXICAN-AMERICAN POPULATION in the United States has generally elevated frequencies of several chronic conditions, including non-insulin-dependent diabetes mellitus (NIDDM), gallbladder disease, and obesity. Prevalence of cardiovascular disease and hypertension is less clear. To document prevalence and risk factors of hypertension in this population, we measured blood pressure in 1004 randomly selected Mexican Americans in Starr County, Texas, ages 15 to 74. We defined hypertension as systolic blood pressure greater than or equal to 140 mmHg or diastolic pressure greater than or equal to 90 mmHg or current (within the last 48 hours) use of antihypertensive medications. Prevalences by age and gender are elevated in this population group compared with those in the general population. In addition to age and gender, body mass and diabetes status were also predictors of hypertension. Comparison of the Starr County results with those reported from the Third National Health and Nutrition Examination Survey (NHANES III) sampling of Mexican Americans indicates a slight increase in frequency of hypertension in Starr County, while comparison with results from San Antonio Mexican Americans indicates a marked increase in frequency in Starr County. These differences are not simple functions of measurement protocols, but are likely to be caused by differences in population structure, employment and socioeconomic status, education, and other such factors.

Adolescent↗
PubMed1995

Linkage studies in NIDDM with markers near the sulphonylurea receptor gene.

The high affinity receptor for sulphonylureas, expressed on the beta cells of the pancreas, plays a crucial role in the control of insulin secretion. Mutations in the cytoplasmic domain of the sulphonylurea receptor (SUR) gene that disrupt the regulation of insulin secretion have been previously described. In the present study, the potential role of genetic variation in the SUR gene has been investigated in non-insulin-dependent diabetes mellitus (NIDDM) through linkage studies with microsatellite markers tightly linked to the SUR gene. The microsatellite markers were typed in 346 Mexican-American NIDDM affected sib pairs derived from 176 families and an additional 110 ethnically and geographically matched control subjects. No evidence of linkage, based on allele sharing, or association based on allele frequencies in patients and control subjects, for any microsatellite marker and NIDDM was observed in this population. These results suggest that genetic variation in the SUR gene does not play a major role in susceptibility to NIDDM in the Mexican-American population.

ATP-Binding Cassette Transporters↗
PubMed1995

Food-frequency questionnaire validation among Mexican-Americans: Starr County, Texas.

A food-frequency questionnaire (FFQ) for low-income Mexican-Americans in Starr County, Texas, was developed as part of an epidemiologic study of gallbladder disease during 1985 and 1986. The FFQ was developed from 7-day food records collected from the first sample. In the validity study, using the second sample, correlations between nutrients calculated from 3-day food records and the FFQ were 0.77, 0.76, and 0.61 for energy, total fat, and saturated fat, respectively. In the reliability study, using the third sample, for the 1-month interval between baseline and a repeat FFQ measurement correlations ranged from 0.90 for energy to 0.85 for total fat and for the 2-month interval they were 0.84 for energy and 0.70 for total fat. The high correlations are largely explained by the lack of diversity in the diets of Starr County individuals which facilitated the high agreement between the FFQ and the food records for estimates of energy, fats, and cholesterol.

Adult↗
PubMed1995

Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM.

The metabolism of glucose in insulin-secreting cells leads to closure of ATP-sensitive K+ channels (KATP), an event that initiates the insulin secretory process. Defects in insulin secretion are a common feature of non-insulin-dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples metabolism and membrane potential is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. We screened a hamster insulinoma cDNA library by low-stringency hybridization with a probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in heart and other tissues. RNA blotting showed that KATP mRNA was present in insulin-secreting cells and brain but not in heart. To assess the contribution of KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was isolated and mapped to chromosome band 21q22.1 by fluorescence in situ hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified in the region of the KATP-2 gene, and linkage studies between this marker and NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is not a major susceptibility gene in this population.

Adenosine Triphosphate↗
PubMed1995

Identification of microsatellite markers near the human ob gene and linkage studies in NIDDM-affected sib pairs.

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex metabolic disorder with a significant genetic component. Obesity is a frequent complicating factor for NIDDM. In the mouse, a number of single gene defects that result in obesity have been described. Mutations in one of these genes, the ob gene, results in both obesity and NIDDM. Recently, the cloning of the murine ob gene and its human homologue has been reported (Nature 372:425-432, 1994). In the present study, the contribution of genetic variation at the human ob locus to NIDDM susceptibility was assessed by analyzing allele sharing in NIDDM-affected sib pairs (ASPs) for markers located near the human ob gene. Four yeast artificial chromosome clones containing the human ob gene were isolated. These clones colocalized the ob gene and two microsatellite markers, D7S514 and D7S635, to a region of 280 kb on the long arm of human chromosome 7. The microsatellite markers were typed in 346 Mexican-American NIDDM-ASPs derived from 176 families and an additional 110 ethnically and geographically matched controls. No evidence of linkage or association between either microsatellite marker and NIDDM was observed in this population. These results suggest genetic variation in the human ob gene does not play a major role in susceptibility to NIDDM in Mexican-Americans.

Animals↗
PubMed1993

Mortality of Mexican Americans with NIDDM. Retinopathy and other predictors in Starr County, Texas.

OBJECTIVE: To determine the rate and risk factors of mortality in a cohort of Mexican Americans with NIDDM. RESEARCH DESIGN AND METHODS: A cohort of 353 Mexican Americans with NIDDM were identified between 1981 and 1986. All individuals underwent extensive evaluations that included physical, historical, ophthalmological, and laboratory assessments. This cohort was followed prospectively for a mean of 8 yr. Follow-up included mortality surveillance, death certificate extraction, and a combination of annual and intermediate examinations. RESULTS: The cohort experienced 67 mortality events. One-third of all deaths were premature < 65 yr of age) and most often were attributed to diseases of the heart (60.0%). In no case was diabetes listed as the cause of death, although it was listed as a contributing cause in 25.5% of cases. Men had a higher mortality rate than women. In both sexes, baseline retinopathy was identified as an important predictor of subsequent mortality. Mortality was significantly elevated in those with nonproliferative retinopathy and even further elevated in those with proliferative disease (relative risks of > or = 4 for proliferative disease). CONCLUSIONS: Mexican Americans with NIDDM are experiencing premature and excessive mortality compared with the general population. The results clearly link microvascular complications with macrovascular disease, but this link is not explained by a more untoward profile of traditional cardiovascular risk factors. Retinopathy appears to serve as an important monitor of the progression of diabetes and when identified would warrant aggressive action to inhibit or slow the processes leading to subsequent mortality.

Age Factors↗
PubMed1993

An ultrasound survey of gallbladder disease among Mexican Americans in Starr County, Texas: frequencies and risk factors.

The Mexican-American population of south Texas has been shown previously to have elevated frequencies of gallbladder disease, based on medical history. In the present study, ultrasonography was employed to screen 1004 randomly selected individuals aged 15 to 74 years. Among women, the frequency of previous cholecystectomy was 10.0%; the frequency of stones on ultrasound was 12.2%. In men, the respective frequencies were 1.7% and 6.3%. Highest frequencies of gallbladder disease occurred among those aged 45 years or above: 40.2% and 19.2% among women and men, respectively. Non-insulin-dependent diabetes mellitus, obesity, and hypertension were also markedly elevated in this population. Overall, more than 40% of the population had either gallbladder disease, non-insulin-dependent diabetes, obesity, or hypertension. Among those older than 45 years, 70% had one or more of these chronic conditions. Examining the associations of gallbladder disease with other chronic diseases or measures of lipids, lipoproteins, and apolipoproteins demonstrates that factors predictive of or associated with cholecystectomy are different from those for gallstones by ultrasound. Diabetes and obesity show the strongest associations with cholecystectomy among women under 45 years (women with diabetes being 6.8 times as likely to have had a cholecystectomy than those without diabetes). Testing an extensive array of lipid-related measures resulted in no clear patterns, with the possible exception of alpha-lipoprotein and related measures. That the Mexican-American population is relatively young and experiencing extremely rapid growth indicates that the burden of chronic disease in general and gallbladder disease in particular will increase dramatically in the coming years.

Adolescent↗
PubMed1992

Juxtaposed short sequence repeat types and haplotypes near exon 3 of the insulin receptor locus among Mexican Americans.

The insulin receptor has been sequenced on numerous occasions and reports suggest several potential polymorphisms, as do a number of reports of single base changes. Examining these reports identifies five potential polymorphisms at or near exon 3. Three of these--codon 233 (CTG to CCG), codon 234 (GAC to GAT), and codon 276 (CAG to CAA)--predict restriction site differences. Just 5' of exon 3, the sequence suggests the presence of two short sequence repeats (SSRs), one with ATTT repeats and one with TC dinucleotide repeats. Amplification of exon 3 using the polymerase chain reaction followed by appropriate restriction digestion demonstrated no variation in a sample of 50 Mexican Americans. The codon 276 results were surprising given several reports showing the putative differences. An additional 91 mixed samples were examined and no variation was detected, suggesting that the reported differences likely resulted from sequencing artifacts. Amplification of a smaller fragment demonstrated 10 phenotypes and 7 alleles for the SSR region. Digestion with MnlI permitted scoring each motif separately and when coupled with the uncut results permits unequivocal classification of haplotypes without familial data. These juxtaposed SSRs should be useful for linkage analysis and investigations of gene structure and evolution.

Alleles↗
PubMed1991

Which measure of body fat distribution is best for epidemiologic research?

Multivariate associations were sought between risk factor levels (total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, glucose, and systolic and diastolic blood pressures) and two sets of anthropometric variables (four circumferences and six skinfolds) to select a set of anthropometric indicators of body fat distribution that correlate most highly with risk of disease. Subjects were men (n = 285) and women (n = 672) from a study of gallbladder disease in a Mexican American population in Starr County, Texas, 1985-1986. The canonical correlations showed that circumferences (0.49-0.61) and skinfolds (0.42-0.60) were equally well correlated to risk factor levels independently of sex and age. Weights from the canonical analyses suggest that measurements at or above the waist and on the lower limb (thigh) are most heavily loaded toward risk (waist = highest risk; thigh = lowest risk). The simplest and most reliable index of body fat distribution for both sexes is the ratio of waist to thigh circumferences. The more commonly used waist/hip ratio proved more valid in women, but not in men. Simple skinfold indices of body fat distribution were more poorly correlated to risk factor levels than the corresponding circumference ratios. In women, body mass index and waist circumference by themselves did as well as body fat distribution indices in explaining variation in risk factors, suggesting the involvement of visceral fat in the body fat/body fat distribution disease relation.

Adipose Tissue↗
PubMed1991

Apolipoprotein A-IV protein polymorphism: frequency and effects on lipids, lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas.

Apolipoprotein A-IV phenotypes were determined by reprobing immunoblots initially typed for the apolipoprotein E polymorphism on a representative sample of Mexican-Americans from South Texas. Typings on 331 individuals gave frequency estimates of 0.928, 0.066, 0.003, and 0.003 for alleles 1, 2, 3, and 4, respectively. To evaluate the effects of this polymorphic variability on lipid-related measures, mean levels between phenotypes were tested for equality following adjustment for age, sex, and body mass index. Analyses of levels of cholesterol, triglycerides, total high density lipoprotein, and its subfractions, low density lipoprotein, alpha and beta lipoproteins and apolipoproteins A-I, A-II, B, C-II, C-III, and E demonstrate that the A-IV genetic variability contributes minimally to normal variation of these quantitative factors in the population. Examination of the rare types, however, indicates the possibility of large metabolic effects whose follow-up may be useful for elucidating the metabolic roles of apolipoprotein A-IV.

Apolipoproteins↗
PubMed1991

Heritability of ventilatory function in smoking and nonsmoking New Mexico Hispanics.

Familial aggregation of ventilatory function has been described in several populations, but the effects of age and cigarette smoking on the extent of aggregation have not been well characterized. We used data from a survey of a Hispanic population in New Mexico to obtain estimates of heritability for FVC and FEV1 as percentages of predicted value. Product-moment correlations for FVC of spouse pairs were 0.18 (n = 90 pairs) if neither smoked, 0.013 (n = 45 pairs) if only the wife smoked, 0.18 (n = 118 pairs) if only the husband smoked, and -0.04 (n = 83 pairs) if both smoked. Correlations for FEV1 of spouse pairs were similar. Because parent-child correlations did not vary with sex, we calculated product-moment correlations from the pooled data. The parent-child correlations for nonsmoking parents with nonsmoking children 6 to 17 yr of age and living in the same house were 0.16 (n = 335 pairs) and 0.17 for FVC and FEV1, respectively. For parents whose children were 25 yr of age or older, the parent-child correlations for those living in different houses were 0.37 (n = 63 pairs) for FVC and 0.40 for FEV1 if neither smoked, and 0.24 (n = 27 pairs) for FVC and 0.14 for FEV1 if both smoked. Heritability estimates, estimated by path analysis, were 0.43 for FVC and 0.42 for FEV1 if neither family member smoked and 0.65 for FVC and 0.44 for FEV1 if both family members smoked. We conclude that there is a moderate degree of heritability of FVC and FEV1 with no substantial change based on age or smoking status.

Age Factors↗
PubMed1991

Signal peptide-length variation in human apolipoprotein B gene. Molecular characteristics and association with plasma glucose levels.

We studied the molecular characteristics of three naturally occurring variants in the human apolipoprotein B (apoB) signal peptide, their frequencies in non-insulin-dependent diabetic and random populations, and their association with several measures of lipid and carbohydrate metabolism. In a random sample of 197 French whites, there were two common alleles, 5'beta SP-24 and 5'beta SP-27, with frequencies of 0.35 and 0.65, respectively. In a random sample of 181 Mexican Americans, there was an additional allele, 5'beta SP-29, with a frequency of 0.03. DNA sequence analysis indicated that the signal peptide alleles consisted of the following: 5'beta SP-29 encoded 29 amino acids in the signal peptide containing two copies of the sequence CTG GCG CTG encoding Leu-Ala-Leu and a consecutive run of eight Leu-encoding codons; 5'beta SP-27 encoded 27 amino acids with a run of only six Leu codons; 5'beta SP-24 encoded 24 amino acids and contained a single copy of CTG GCG CTG and a run of six Leu codons. In the sample of French whites, average apoAI and glucose levels were significantly different among signal peptide genotypes. 5'beta SP-24/24 homozygotes had higher apoAI levels than the two other signal peptide genotypes (1.59 vs. 1.42 g/L, respectively). Heterozygous 5'beta SP-24/27 individuals had the highest glucose levels. In the random sample of Mexican Americans, average glucose levels were also significantly different among signal peptide genotypes. However, the rank order of average glucose levels was not the same between the two samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM subjects.

We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in Starr County, Texas, for the three common apolipoprotein E (apoE) alleles. Typing was performed via DNA amplification and Hha I restriction. The allele frequencies (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from the same population (chi 2 = 0.16, df = 2). Analysis of variance was used to test for mean differences in lipid, lipoprotein, and glucose levels among apoE types. Significant differences among types were detected for low-density lipoprotein cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P = 0.019, R2 = 3.3) levels. Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was 3.26 mM, and E4/3 was 3.36 mM. Mean beta-lipoprotein cholesterol in E2/3 individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM. Based on these results, we conclude that the effects of the apoE polymorphism on lipid profiles and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican Americans and other populations. Other studies investigating the role of apoE polymorphism in diabetic subjects have found increased triglyceride levels in individuals possessing an epsilon 2-allele and an increased frequency of the epsilon 2-allele in hyperlipidemic diabetic subjects. We found no significant difference in mean triglyceride levels among genotypes. Possible reasons for this discrepancy are discussed, including DNA- versus protein-typing methods.

Apolipoproteins E↗
PubMed1991

Origins of U.S. Hispanics. Implications for diabetes.

The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implications of these origins in the context of diabetes risk. Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups, i.e., Mexican Americans, Puerto Ricans, and Cubans. The U.S. Census figures provided basic demographic information. Genetic marker data for ancestral populations were taken from a review of the literature and compendia. Genetic marker data for the Puerto Rican and Cuban populations were extracted from the literature. Genetic markers determined on approximately 1000 randomly selected Mexican Americans from Starr County, Texas, were taken as representative of the Mexican-American population. The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents, of whom 62% were classified as Mexican, 13% as Puerto Rican, and the remaining 25% as Cubans and others. Various lines of evidence can be used to characterize the Hispanic population and its origins. These include ethnohistory, self-assessment of ancestry, surname distributions, speech and cultural characteristics, quantitative traits, and genetic structure. Genetic data were used to estimate the contribution of putative ancestral populations to the contemporary gene pool. For Mexican Americans, 31% of the contemporary gene pool is estimated to be Native American derived, whereas 61 and 8% are Spanish and African derived, respectively. In Puerto Rico, the percentage of contributions of Spanish, Native American, and African admixture to the population are 45, 18, and 37%, respectively. For Cuba, the parallel estimates are 62, 18, and 20%. The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology. Our results are consistent with the finding of the significant role of genes in determining risk.

Adolescent↗