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Biomedical subjects

Jean W MacCluer

Publications and source records attributed to Jean W MacCluer.

At least 37 records · Page 2Linked to original sources
PubMed2004

Heritability of left ventricular dimensions and mass in American Indians: The Strong Heart Study.

OBJECTIVE: We sought to determine the heritability of left ventricular dimensions and mass in adult American Indians. METHODS: Echocardiograms were analysed in 1373 American Indian participants, from 445 families, in the Strong Heart Study (SHS) to determine the heritability of left ventricular dimensions and mass. Heritability calculations were performed using variance component analysis in SOLAR, a computer analysis program. RESULTS: The SHS participants analysed in this study included 1305 relative pairs, predominantly (n = 1077) sib-pairs. After simultaneously adjusting for sex, age and centre, the proportion of the residual phenotypic variance due to additive genetic effects or heritability (h2) of left ventricular mass was 0.27 (SE = 0.08, P < 0.001). Addition of body weight, height, systolic blood pressure, heart rate, medications and diabetes into the polygenic model attenuated the residual h2 of left ventricular mass to 0.17 (SE = 0.09, P < 0.05). The residual h2 for left ventricular end-diastolic chamber diameter (LVID), after simultaneously adjusting for sex, age and centre was 0.36 (SE = 0.08, P < 0.001) for the analysed families. The residual h2 for interventricular septal wall thickness was 0.26 (SE = 0.07), while that of left ventricular posterior wall thickness was 0.19 (SE = 0.08, both P < 0.001). While adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes reduced the h2 of LVID to 0.33 (SE = 0.09, P < 0.001), the h2 of septal (0.12, SE = 0.10) and posterior wall thickness (0.09, SE = 0.09) were no longer significant after similar adjustment. The residual h2 for relative wall thickness, a measure of left ventricular geometry, was 0.22 (SE = 0.07, P < 0.001) after adjusting for sex, age and centre, and 0.17 (SE = 0.08, P < 0.05) after additional adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes. CONCLUSIONS: A substantial proportion of the variance of left ventricular dimensions and mass can be explained by heredity, independent of the effects of sex, age, body size, blood pressure, heart rate, medications and diabetes. Identification of genes influencing left ventricular size and geometry may provide mechanistic and therapeutic targets to prevent left ventricular hypertrophy.

Aged↗
PubMed2004

Principal component for metabolic syndrome risk maps to chromosome 4p in Mexican Americans: the San Antonio Family Heart Study.

Metabolic syndrome refers to the clustering of disease conditions such as insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and obesity. To explore the genetic predispositions of this complex syndrome, we conducted a principal components analysis using data on 14 phenotypes related to the risk of developing metabolic syndrome. The subjects were 566 nondiabetic Mexican Americans, distributed in 41 extended families from the San Antonio Family Heart Study. The factor scores obtained from these 14 phenotypes were used in multipoint linkage analysis using SOLAR. Factors were identified that accounted for 73% of the total variance of the original variables: body size-adiposity, insulin-glucose, blood pressure, and lipid levels. Each factor exhibited evidence for either significant or suggestive linkage involving four factor-specific chromosomal regions relating to chromosomes 1, 3, 4, and 6. Significant evidence for linkage of the lipid factor was found on chromosome 4 near marker D4S403 (LOD = 3.52), where the cholecystokinin A receptor (CCKAR) and ADP-ribosyl cyclase 1 (CD38) genes are located. Suggestive evidence for linkage of the body size-adiposity factor to chromosome 1 near marker D1S1597 (LOD = 2.53) in the region containing the nuclear receptor subfamily 0, group B, member 2 gene (NROB2) also was observed. The insulin-glucose and blood pressure factors were linked suggestively to regions on chromosome 3 near marker D3S1595 (LOD = 2.20) and on chromosome 6 near marker D6S 1031 (LOD = 2.08), respectively. In summary, our findings suggest that the factor structures for the risk of metabolic syndrome are influenced by multiple distinct genes across the genome.

Adult↗
PubMed2004

Gene by smoking interaction: evidence for effects on low-density lipoprotein size and plasma levels of triglyceride and high-density lipoprotein cholesterol.

We seek to determine whether significant gene x smoking interaction effects exist on plasma triglyceride (TG) levels, HDL cholesterol (HDL-C) level, and median LDL particle diameter (LDL-MPD) in Mexican American families enrolled in the San Antonio Family Heart Study. The sample consisted of 1,392 individuals distributed in 42 extended pedigrees, ranging in age from 16 years to 92 years. Separate quantitative genetic analyses were carried out for TG and HDL-C level and LDL-MPD using a maximum-likelihood-based variance decomposition approach while simultaneously adjusting for age and sex. Initial heritability estimates demonstrated significant (p < 0.001) additive genetic contributions to all three traits (h2 range 0.50 - 0.54). To test for a gene x smoking interaction, we included in the model additional smoking-status-specific variance terms and a genetic correlation term between smokers and nonsmokers. Comparisons of nested models revealed significant evidence (p < 0.01) for a gene X smoking interaction effect on TG level and LDL-MPD and possible evidence for an effect on HDL-C level. These results indicate that the gene or suite of genes regulating each of these phenotypes is likely the same in smokers and non-smokers but that smoking may alter the expression of genes, particularly those influencing TG level and LDL-MPD.

Adolescent↗
PubMed2004

Intercellular adhesion molecule-1 concentration is genetically correlated with insulin resistance, obesity, and HDL concentration in Mexican Americans.

The metabolic syndrome and type 2 diabetes are associated with endothelial activation (and thus with inflammatory processes leading to atherosclerosis), but the mechanisms that underlie these associations are not fully understood. Endothelial intercellular adhesion molecule (ICAM)-1 plays an important role in the recruitment of immune cells during the development of atherosclerotic plaque and is a marker of inflammatory disease. We performed bivariate quantitative genetic analyses to estimate genetic and environmental correlations between circulating ICAM-1 concentration and 17 phenotypes associated with the metabolic syndrome. Our study population comprised 428 adults in 20 extended Mexican-American families from the San Antonio Family Heart Study (SAFHS). Circulating ICAM-1 concentration is heritable (h(2) = 0.56). ICAM-1 concentration showed significant positive genetic correlations (range 0.32-0.52, P < 0.05) with fasting insulin, insulin 2 h after oral glucose challenge, homeostasis model assessment of insulin resistance, BMI, waist circumference, and leptin concentration; negative genetic correlation with HDL3 cholesterol concentration; and negative environmental correlation with adiponectin concentration. Significant genetic correlations were not found between ICAM-1 and fasting or 2-h serum glucose or systolic or diastolic blood pressure. Thus, ICAM-1 expression may share common genetic modulation with traits related to obesity, insulin resistance, and HDL3 cholesterol, but not with hyperglycemia or hypertension per se.

Blood Glucose↗
PubMed2004

Genome-wide scans reveal quantitative trait Loci on 8p and 13q related to insulin action and glucose metabolism: the San Antonio Family Heart Study.

Type 2 diabetes is a complex disease that arises from physiological disruptions of the body's sensitivity to insulin and ability to metabolize glucose. Multipoint linkage analyses for insulin sensitivity phenotypes were conducted in 1,280 Mexican Americans from 41 families who participated in the San Antonio Family Heart Study. A significant linkage signal (logarithm of odds [LOD] = 2.98) affecting corrected insulin response to glucose was detected on chromosome 13q between D13787 and D13S252, in the region where the MODY-4 gene has previously been mapped. Another signal on chromosome 13 was observed at D13S285 (LOD = 1.86), where the insulin receptor substrate 2 gene resides. Significant linkage (LOD = 3.09) for insulin response to glucose was found on chromosome 8 between D8S1130 and D8S1106, near the lipoprotein lipase and macrophage scavenger receptor genes. Multipoint analysis of abdominal skinfold with an LOD of 2.68 showed signals in the same region. There was also suggestive evidence for linkage of quantitative insulin sensitivity check index and fasting glucose to a previously reported location at D9S301 (LOD = 2.19). These results indicate that chromosomal locations on 8p and 13q might harbor genes that affect a variety of insulin- and glucose-related phenotypes that contribute to the observed variations in these important risk factors for diabetes in Mexican Americans.

Adult↗
PubMed2003

Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study.

The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study (conducted between 1998 and 1999) and evaluate the heritabilities of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes.

Adult↗
PubMed2003

Evidence for genetic factors underlying the insulin resistance syndrome in american indians.

Previous analyses of American Indians of the Strong Heart Study have demonstrated that various insulin-resistance variables cluster, although knowledge about the genetic determination of these clusters is unknown. In an effort to explore the influences on the aggregation of insulin-resistance phenotypes, we used principal component factor analysis to examine the clustering of these phenotypes in participants of the Strong Heart Family Study and evaluated the genetic and environmental contributions of such factors. Nine traits were chosen for principal component factor analysis: BMI, diastolic blood pressure, fasting glucose, high-density lipoprotein-cholesterol, natural log-transformed insulin, natural log-transformed triglycerides, percentage of body fat, systolic blood pressure, and waist-to-hip ratio. Analyses revealed three clusters: glucose/insulin/obesity, blood pressure, and dyslipidemia factors. Using a variance component approach and accounting for the effects of age, sex, center, and medication, we detected significant heritabilities (h2) for the three factors: h2 = 0.67, h2 = 0.33, and h2 = 0.61, respectively. In multivariate analysis, no significant genetic correlations among factors were found. These results suggest that heredity explains a substantial proportion of the variability of the factors that underlie the insulin resistance syndrome in American Indians and that these factors are genetically independent.

Aged↗
PubMed2003

Epidemic of diabetic and nondiabetic renal disease among the Zuni Indians: the Zuni Kidney Project.

There is an epidemic of renal disease among the Zuni Indians. The prevalence of end-stage renal disease among the Zuni Indians is 18.4-fold and 7.4-fold higher than among European Americans and American Indians/Alaskan Natives, respectively. In contrast to other American Indian tribes, nondiabetic renal disease accounts for a significant percent of the renal disease burden among the Zuni Indians. To explore this hypothesis, a community epidemiologic study of the Zuni Pueblo was conducted. A questionnaire was administered, blood and urine samples were collected, and BP, height, and weight were measured. Neighborhood household clusters were used as the sampling frame to maximize ascertainment and minimize bias. Age and gender distributions in the sample (n = 1483) were similar to those of the eligible Zuni population (n = 9228). The prevalence, age-adjusted and gender-adjusted to the Zuni population, of incipient (0.03 < or = UACR < 0.3) albuminuria (IA) (15.0% [95% confidence interval, 13.1 to 16.9%]), and overt (UACR > or = 0.3) albuminuria (OA) (4.7% [3.6 to 5.8%]) was high. The prevalence estimates for IA and OA were higher among diabetic participants (IA: 33.6% [27.6 to 39.7%]; OA: 18.7% [13.7 to 23.7%]) than nondiabetic participants (IA: 10.8% [9.0 to 12.6%]; OA: 1.8% [1.0 to 2.5%]). However, there were more nondiabetic participants; therefore, they comprised 58.0% [51.4 to 64.6%] and 30.9% [20.0 to 41.7%] of participants with IA and OA, respectively. In contrast to most other American Indian tribes, nondiabetic renal disease contributes significantly to the overall burden of renal disease among the Zuni Indians.

Adolescent↗
PubMed2003

The Zuni kidney project: a collaborative approach to an epidemic of kidney disease.

There is an epidemic of renal disease among the Zuni Indians. In contrast to most other American-Indian communities, the epidemic of renal disease among the Zuni Indians reflects high rates of diabetic and nondiabetic renal disease. Almost every Zuni Indian has a relative with end-stage renal disease. This epidemic offers a unique opportunity to advance our understanding of the risk factors for the susceptibility and/or progression of renal disease. Thus, Zuni Tribal leaders formed a research partnership with the University of New Mexico Health Sciences Center, Indian Health Service, Southwest Foundation for Biomedical Research and Dialysis Clinic Inc., to establish the Zuni Kidney Project (ZKP). The ZKP conducted a population-based, cross-sectional survey of the Zuni Pueblo. Age and gender distributions among survey participants were similar to those of the eligible Zuni population. Among diabetics the prevalence (95% confidence interval) of incipient albuminuria (IA) was 32.3% (25.1, 39.5) in women and 36.1% (24.7, 47.5) in men. The prevalence of IA among nondiabetics was 9.3% (6.9, 11.7) in women and 12.2% (9.7, 14.7) in men. Among diabetics, the prevalence of overt albuminuria (OA) was 17.7% (11.9, 23.5) in women and 20.8% (11.4, 30.2) in men. Among nondiabetics, OA was present in 1.2% (0.3, 2.1) of women and 2.3% (1.1, 3.5) of men. Although IA and OA were each more common among diabetics, the majority of participants with albuminuria were nondiabetics. Hematuria was common among both diabetics and nondiabetics. Among diabetics, the crude prevalence of hematuria was similar among men and women. Among nondiabetics, however, hematuria was more common among women. Diabetes and obesity were more common among women than men. In contrast, hypertension and hypercholesterolemia were more common among men than women. The ZKP is incorporating these preliminary data into planning for the development and implementation of primary and secondary prevention programs.

Adolescent↗
PubMed2003

The genetics of obesity in Mexican Americans: the evidence from genome scanning efforts in the San Antonio family heart study.

Recent estimates indicate that approximately 18% of the population in the United States can be considered obese (defined as a body mass index [BMI] > or = 30), and this rate is even higher among ethnic populations such as Mexican Americans. This figure becomes very significant given the strong evidence for obesity as a major risk factor for a variety of chronic diseases including type 2 diabetes mellitus and coronary heart disease. The search for genes involved in the expression of obesity has been one of the focal points of the San Antonio Family Heart Study (SAFHS), a large, family-based study to examine the genetics of risk for atherosclerosis in Mexican Americans. To date, our genome scanning effort has reported two quantitative trait loci (QTLs) with pronounced effects on the expression of a variety of obesity--related phenotypes (e.g., leptin levels, fat mass, and BMI) located on chromosomes 2 and 8. We are currently working to further refine these signals and to identify the genes and allelic variants involved. Here, we summarize the latest results from our ongoing efforts to identify obesity genes in the San Antonio Family Heart Study.

Adult↗
PubMed2003

Prevalence of diabetes is higher among female than male Zuni indians.

OBJECTIVE: Test the hypothesis that diabetes and related risk factors are more common among female than male Zuni Indians. RESEARCH DESIGN AND METHODS: We conducted a population-based, cross-sectional survey of the Zuni Indians aged > or =5 years. We used households within neighborhood clusters as the sampling frame. We administered a questionnaire, collected blood and urine, and measured height and weight. Self-reported diabetes was used to assess previously diagnosed diabetes. Participants without a prior history of diabetes were classified as having newly diagnosed diabetes if they had HbA(1c) >7.0% or random glucose > or =11.1 mmol/l during the survey. RESULTS: The prevalence of previously diagnosed diabetes among Zuni Indians aged > or =5 years (n = 1,503) was higher among female Zuni Indians (16.7% [95% CI 14.1-19.3]) than male Zuni Indians (9.7% [7.4-12.1]) (P < 0.001). The prevalence of newly diagnosed diabetes was similar among female Zuni Indians (2.4% [1.4-3.4]) and male Zuni Indians (2.4% [1.2-3.6]). The prevalence of previously and newly diagnosed diabetes was higher among female Zuni Indians (19.1% [16.4-21.9]) than male Zuni Indians (12.2% [9.5-14.8]) (P < 0.001). The prevalence of obesity was higher among female Zuni Indians (34.3% [30.9-37.7]) than male Zuni Indians (21.5% [18.4-24.7]) (P < 0.001). Obesity was associated with diabetes among female and male Zuni Indians. Physical inactivity was more common among female Zuni Indians (44.2% [40.7-47.8]) than male Zuni Indians (35.1% [31.5-38.7]) (P < 0.001). However, physical inactivity was not associated with diabetes among either female or male Zuni Indians. Gestational diabetes was a risk factor among female Zuni Indians. CONCLUSIONS: Among the Zuni Indians, the prevalence of diabetes was 57% higher among female than male members of the population. Culture, tradition, and lifestyle differences may contribute to the higher prevalence of diabetes and obesity among female Zuni Indians.

Adolescent↗
PubMed2002

Heritability of carotid artery structure and function: the Strong Heart Family Study.

OBJECTIVE: Alterations in carotid artery structure and function may represent phenotypic measures of vascular disease that contain information beyond that which can be inferred from conventional cardiovascular disease risk assessment. However, apart from their associations with cardiovascular disease risk factors and outcome, the genetic basis of variations in carotid artery structure and function is largely unknown. The purpose of this study was to examine the genetic and environmental contributions to carotid artery structure and function in 3 large groups of American Indians. METHODS AND RESULTS: Approximately 950 men and women, aged > or =18 years, in 32 extended families were examined between 1997 and 1999. By use of a variance component approach and the program Sequential Oligogenic Linkage Analysis Routines, heritabilities for carotid artery structure and function phenotypes were estimated. After accounting for the effects of covariates (sex, age, diabetes, impaired glucose tolerance, smoking, cholesterol, body surface area, and hypertension), we detected significant heritabilities (given as h2 values) for common carotid artery diastolic diameter (h2<0.44), intimal-medial wall thickness (h2<0.21), vascular mass (h2<0.27), arterial stiffness (h2<0.23), and the augmentation index (h2<0.18). CONCLUSIONS: These results suggest that the additive effects of genes explain a moderate proportion of the variability of carotid artery structure and function.

Aged↗
PubMed2002

Genetic influences on aortic root size in American Indians: the Strong Heart Study .

Aortic root dilatation is a major pathophysiological mechanism for aortic regurgitation and predisposes the aortic root to dissection or rupture. However, only a small proportion of the variance of aortic root size can be explained by its known clinical and demographic correlates. The present study was undertaken to determine the heritability of echocardiographically derived aortic root diameter in the American Indian participants in the second Strong Heart Study examination. Echocardiograms were analyzed in 1373 SHS participants who had > or =1 family member in the cohort. Heritability calculations were performed by using variance component analysis as implemented in SOLAR, a computer analysis program. In a polygenic model, the variables entered and identified as covariates of larger aortic root diameter were older age, male sex, and center (P<0.001), which accounted for 35% of the overall variability of aortic root diameter. After simultaneous adjustment was made for these significant covariates, the proportion of phenotypic variance due to additive genetic contribution or residual heritability (h2) was 0.51 (SE=0.08, P<0.001). Additionally, simultaneous adjustment for height, weight, and systolic and diastolic BPs yielded slightly lower residual h2 of aortic root diameter (h2=0.44, SE=0.08, P<0.001), which accounted for 26% of the overall variance of aortic root size. Because center effects were identified as significant covariates in the analyses, h2 analyses were performed separately in Arizona, Oklahoma, and North/South Dakota centers, which confirmed that a significant proportion of the phenotypic variance of aortic root diameter is due to additive genetic contribution. Heredity explains a substantial proportion of the variability of aortic root size that is not accounted for by age, sex, body size, and blood pressure. Echocardiographic screening of family members with aortic root dilatation may identify other individuals predisposed to aortic dissection or rupture.

Aged↗
PubMed2002

Leptin's sexual dimorphism results from genotype by sex interactions mediated by testosterone.

OBJECTIVE: Recent studies have reported the existence of marked sexual dimorphism in serum leptin levels in humans, with women having approximately three times the levels of men. As we have shown for other measures of adiposity, such sexual dimorphism can arise from a special case of genotype by environment interaction, that of genotype by sex interaction. RESEARCH METHODS AND PROCEDURES: Using maximum likelihood-based variance decomposition techniques, we examined the genetic and environmental architecture of sexual dimorphism in serum leptin levels in 1147 Mexican Americans from the San Antonio Family Heart Study. RESULTS: Both the genetic and environmental variances for this trait differed significantly between the sexes (p < 0.001 and p < 0.01, respectively), with women displaying larger values for both components. We found significant evidence that different genes influence variation in serum leptin levels between the two sexes (p = 0.05). Furthermore, this pattern of sexual dimorphism in serum leptin levels persisted even after accounting for the effects of either the percentage of body fat or total body fat. However, this pattern of sexual dimorphism was eliminated after accounting for the effects of testosterone. DISCUSSION: These findings suggest that the sexual dimorphism seen in leptin levels is not simply explained as differences in total adiposity between the sexes. We conclude that the genes, which influence variation in serum leptin levels, are differentially expressed depending on sex, and that the sexes also show differences in response of the expression of this obesity-related trait to unmeasured residual effects.

Adipose Tissue↗
PubMed2002

A quantitative trait locus on chromosome 22 for serum leptin levels adjusted for serum testosterone.

OBJECTIVE: Studies have reported the existence of marked sexual dimorphism in serum leptin levels in humans with women having approximately two to three times the levels of men. We have shown that this sexual dimorphism has a strong genetic component arising from a genotype by sex interaction, but adjusting leptin levels for testosterone eliminates this interaction. Because interactions such as genotype x sex can confound the detection of quantitative trait loci (QTLs), we wanted to determine if there are QTLs associated with the expression of leptin adjusted for testosterone. RESEARCH METHODS AND PROCEDURES: We performed a genome-wide scan using multipoint linkage analysis and implemented a general pedigree-based variance-component approach to identify genes with measurable effects on variation in leptin levels independent of testosterone in 318 Mexican Americans from the San Antonio Family Heart Study. RESULTS: We detected significant evidence of linkage (log of the odds ratio = 3.44) for a QTL on chromosome 22. DISCUSSION: Given these results, we hypothesize that a QTL on chromosome 22 may influence the level of leptin adjusted for testosterone.

Adult↗
PubMed2002

A population-based, cross-sectional survey of the Zuni Pueblo: a collaborative approach to an epidemic of kidney disease.

Approximately 80% of the Zuni Indians live in Zuni Pueblo in rural New Mexico. The Zuni are relatively endogamous and differ culturally and ethnically from neighboring tribes. The Zuni Pueblo is experiencing an epidemic of renal disease. The prevalence of end-stage renal disease (ESRD) among the Zuni Indians, adjusted for age and gender, is 6-fold and 21-fold higher than the prevalence rates for Native Americans and European Americans. Almost all Zuni tribal members have a relative with ESRD. This has led to strong public support for renal research. In response, the Zuni community has partnered with the Indian Health Service (IHS), University of New Mexico Health Sciences Center (UNMHSC), Southwest Foundation for Biomedical Research (SFBR), Dialysis Clinic Inc (DCI), and the National Institutes of Health (NIH) to establish a research consortium, the Zuni Kidney Project (ZKP). The goal of the ZKP is to reduce the burden of renal disease in the Zuni community. The ZKP combines traditional, population-based, epidemiologic methods with modern techniques of population genetics. The foundation of the ZKP is a population-based, cross-sectional survey (PBCSS). The PBCSS has 3 specific aims: (1) estimate the prevalence of renal disease in Zuni; (2) assess risk factors for renal disease susceptibility; and (3) identify participants for planned case-control, longitudinal cohort, and family studies designed to identify environmental, familial, and genetic risk factors for the susceptibility and/or progression of renal disease. Preliminary results of the PBCSS confirm that the epidemic of renal disease in Zuni Indians is due to high rates of both diabetic and nondiabetic renal disease.

Adolescent↗
PubMed2001

Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans.

High-density lipoproteins (HDLs) are anti-atherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed. Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with an increased incidence of coronary heart disease and an increased mortality rate, indicating a protective role of high concentrations of HDL-C against atherogenesis and the development of coronary heart disease. HDL-C level is influenced by several genetic and nongenetic factors. Nongenetic factors include smoking, which has been shown to decrease the HDL-C level. Exercise and alcohol have been shown to increase HDL-C levels. Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia and hypertension. Although several genes have been identified for rare forms of dyslipidemia, the genes accounting for major variation in HDL-C levels have yet to be identified. Using a multipoint variance components linkage approach, we found strong evidence of linkage (lod score=3.4; P=0.00004) of a quantitative trait locus (QTL) for HDL-C level to a genetic location between markers D9S925 and D9S741 on chromosome 9p in Mexican Americans. A replication study in an independent set of Mexican American families confirmed the existence of a QTL on chromosome 9p.

Adult↗