Biomedical subjects

M A Austin

Publications and source records attributed to M A Austin.

At least 37 records · Page 2Linked to original sources

PubMed1999

Linkage analysis of candidate genes and the small, dense low-density lipoprotein phenotype.

There is accumulating evidence for the importance of small, dense low-density lipoprotein (LDL), the defining feature of the atherogenic lipoprotein phenotype, as a risk factor for coronary heart disease. Although both family studies and twin studies have demonstrated genetic influences on this phenotype, the specific gene(s) involved remain to be identified. The purpose of this study was to determine whether there was evidence for genetic linkage between small, dense LDL (LDL subclass phenotype B), as determined by gradient gel electrophoresis, and selected candidate genes known to be involved in lipid metabolism. The linkage analyses were based on a sample of 19 families, including 142 individual family members, using a lod score linkage analysis approach. Nine candidate genes were examined, including loci for manganese superoxide dismutase (Mn SOD2), apolipoproteins CIII, AII, and apo CII, lipoprotein lipase, hepatic lipase, microsomal triglyceride transport protein, the insulin receptor and the LDL receptor. The analyses did not provide significant evidence for genetic linkage between markers for any of these genes and LDL subclass phenotype B, nor did it confirm previous reports of linkage between the LDL receptor gene and LDL subclass phenotype B. Using three closely linked markers for the Mn SOD2 locus excluded close linkage between this candidate gene region and LDL subclass phenotype B. These findings demonstrate the complexity of genetically mapping risk factor phenotypes, and emphasize the necessity of identifying new genetic loci, other than known candidate genes, involved in susceptibility to atherosclerosis.

Apolipoproteins↗

PubMed1999

Linkage of low-density lipoprotein size to the lipoprotein lipase gene in heterozygous lipoprotein lipase deficiency.

Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in the LpL gene. LDL particle size was smaller among the heterozygous subjects, compared with controls. Among heterozygous subjects, 44% were classified as affected by LDL subclass phenotype B, compared with 8% of normal family members. Plasma triglyceride levels were significantly higher, and high-density lipoprotein cholesterol (HDL-C) levels were lower, in heterozygous subjects, compared with normal subjects, after age and sex adjustment. A highly significant LOD score of 6.24 at straight theta=0 was obtained for linkage of LDL particle size to the LpL gene, after adjustment of LDL particle size for within-genotype variance resulting from triglyceride and HDL-C. Failure to adjust for this variance led to only a modest positive LOD score of 1.54 at straight theta=0. Classifying small LDL particles as a qualitative trait (LDL subclass phenotype B) provided only suggestive evidence for linkage to the LpL gene (LOD=1. 65 at straight theta=0). Thus, use of the quantitative trait adjusted for within-genotype variance, resulting from physiologic covariates, was crucial for detection of significant evidence of linkage in this study. These results indicate that heterozygous LpL deficiency may be one cause of small LDL particles and may provide a potential mechanism for the increase in coronary disease seen in heterozygous LpL deficiency. This study also demonstrates a successful strategy of genotypic specific adjustment of complex traits in mapping a quantitative trait locus.

Adolescent↗

PubMed1999

Pleiotropic genetic effects on LDL size, plasma triglyceride, and HDL cholesterol in families.

The interrelationships among low density lipoprotein (LDL) particle size, plasma triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) are well established and may involve underlying genetic influences. This study evaluated common genetic effects on LDL size, TG, and HDL-C by using data from 85 kindreds participating in the Genetic Epidemiology of Hypertriglyceridemia (GET) Study. A multivariate, maximum likelihood-based approach to quantitative genetic analysis was used to estimate the additive effects of shared genes and shared, unmeasured nongenetic factors on variation in LDL size and in plasma levels of TG and HDL-C. A significant (P<0.001) proportion of the variance in each trait was attributable to the additive effects of genes. Maximum-likelihood estimates of heritability were 0.34 for LDL size, 0.41 for TG, and 0.54 for HDL-C. Significant (P<0.001) additive genetic correlations (rho(G)), indicative of the shared additive effects of genes on pairs of traits, were estimated between all 3 trait pairs: for LDL size and TG rho(G)=-0.87, for LDL size and HDL-C rho(G)=0.65, and for HDL-C and TG rho(G)=-0.54. A similar pattern of significant environmental correlations between the 3 trait pairs was also observed. These results suggest that a large proportion of the well-documented correlations in LDL size, TG, and HDL-C are likely attributable to the influence of the same gene(s) in these families. That is, the gene(s) that may contribute to decreases in LDL size also contribute significantly to higher plasma levels of TG and lower plasma levels of HDL-C. These relationships may be useful in identifying genes responsible for the associations between these phenotypes and susceptibility to cardiovascular disease in these families.

Adult↗

PubMed1999

LDL size and risk of coronary heart disease in elderly men and women.

A predominance of small, dense, low density lipoprotein (LDL) particles has consistently been associated with coronary heart disease (CHD) in young and middle-aged subjects in cross-sectional studies. Recently, 3 prospective, case-control studies showed that decreased LDL size is a predictor of CHD in middle-aged subjects. However, it is not known whether decreased LDL size is mainly associated with premature CHD or whether it continues to play a role in CHD risk at older ages also. We performed a prospective, nested case-control study in 86 subjects (58 nondiabetic and 28 type 2 diabetic) aged 65 to 74 years who were free of myocardial infarction at baseline and who then had a myocardial infarction or CHD death during a 3.5-year follow-up (cases) and in 172 controls matched for sex and diabetes status but who remained free of CHD during follow-up. LDL particle size determined by gradient gel electrophoresis (268.2+/-0.9 versus 268.5+/-0.7 A, P=0.782) and the proportion of subjects with LDL subclass phenotype B (20.9 versus 21. 5, P=0.914) were similar among cases and controls. Furthermore, diastolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A(1), fasting glucose, fasting insulin, waist-to-hip ratio, and body mass index were not associated with CHD risk. However, smoking and increased systolic blood pressure, apolipoprotein B levels, and the total cholesterol-high density lipoprotein cholesterol ratio were significant predictors of CHD events both in univariate and multivariate analyses. Our findings indicate that LDL size is not a predictor of CHD events in elderly white subjects after controlling for diabetes status.

Aged↗

PubMed1998

Factors of the insulin resistance syndrome in nondiabetic and diabetic elderly Japanese-American men.

Factor analysis has previously identified four independent factors that characterize the insulin resistance syndrome in women, interpreted as 1) weight/waist, 2) lipids, 3) insulin/glucose, and 4) systolic and diastolic blood pressure. Because it is not known whether similar factors emerge for men, or for diabetics, factor analysis was used to investigate the clustering of features characterizing the insulin resistance syndrome using data from 3,159 elderly (71-93 years) Japanese-American men participating in the fourth examination of the Honolulu Heart Program during 1991-1993. Consistent with previous results, factor analysis reduced eight risk factors (insulin, glucose, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, weight, and waist circumference) to four uncorrelated factors that explained 78.2% and 74.7% of the variance in nondiabetics (n = 2,760) and diabetics (n = 399), respectively. These factors were interpreted as 1) weight/waist, 2) blood pressure, 3) lipids, and 4) insulin/glucose. Modest differences in the associations between fasting insulin and factors 1, 3, and 4 were noted for diabetics. These consistently identified composite factors may represent markers for underlying pathophysiologic mechanisms of the insulin resistance syndrome and risk of non-insulin-dependent diabetes mellitus.

Aged↗

PubMed1998

Hypertriglyceridemia as a cardiovascular risk factor.

To determine the relation between plasma triglyceride levels and the risk of incident cardiovascular disease, the semiquantitative techniques of meta-analysis were applied to 17 population-based prospective studies of triglyceride and cardiovascular disease. Sixteen of these studies represented 2,445 events among 46,413 Caucasian men followed for an average period of 8.4 years, and 5 studies represented 439 events among 10,864 Caucasian women followed for an average period of 11.4 years. Univariate relative risk (RR) estimates for incident cardiovascular disease associated with a 1-mmol/L increase in triglyceride was 1.07-1.98 in men, with a summary RR of 1.32 (95% confidence interval [CI]: 1.26-1.39), indicating a 32% increase in disease risk associated with increased triglyceride. In the studies involving women, individual RR estimates for triglyceride were 1.69-2.05, with a summary RR of 1.76 (95% CI: 1.50-2.07), indicating a 76% increase in disease risk associated with increased triglyceride. After adjustment for high-density lipoprotein cholesterol and other risk factors, these risks were decreased to 14% in men and 37% in women but remained statistically significant. Three recent prospective epidemiologic studies have also shown that plasma triglyceride and low-density lipoprotein particle size predict subsequent coronary artery disease in Caucasian populations. Taken together, these studies demonstrate the importance of triglyceride levels as a risk factor for cardiovascular disease.

Cardiovascular Diseases↗

PubMed1998

Family history as a risk factor for primary cardiac arrest.

BACKGROUND: The hypothesis that a family history of myocardial infarction (MI) or primary cardiac arrest (PCA) is an independent risk factor for primary cardiac arrest was examined in a population-based case-control study. In addition, we investigated whether recognized risk factors account for the familial aggregation of these cardiovascular events. METHODS AND RESULTS: PCA cases, 25 to 74 years old, attended by paramedics during the period 1988 to 1994 and population-based control subjects matched for age and sex were identified from the community by random digit dialing. All subjects were free of recognized clinical heart disease and major comorbidity. A detailed history of MI and PCA in first-degree relatives was collected in interviews with the spouses of case and control subjects by trained interviewers using a standardized questionnaire. For each familial relationship, there was a higher rate of MI or primary cardiac arrest (MI/PCA) in relatives of case compared with relatives of control subjects. Overall, the rate of MI/PCA among first-degree relatives of cardiac arrest patients was almost 50% higher than that in first-degree relatives of control subjects (rate ratio [RR]=1.46; 95% CI=1.23 to 1.72). In a multivariate logistic model, family history of MI/PCA was associated with PCA (RR=1.57; 95% CI=1.27 to 1.95) even after adjustment for other common risk factors. CONCLUSIONS: Family history of MI or PCA is positively associated with the risk of primary cardiac arrest. This association is mostly independent of familial aggregation of other common risk factors.

Aged↗

PubMed1998

Candidate-gene studies of the atherogenic lipoprotein phenotype: a sib-pair linkage analysis of DZ women twins.

There is a growing body of evidence supporting the roles of small, dense LDL and plasma triglyceride (TG), both features of the atherogenic lipoprotein phenotype, as risk factors for coronary heart disease. Although family studies and twin studies have demonstrated genetic influences on these risk factors, the specific genes involved remain to be determined definitively. The purpose of this study was to investigate genetic linkage between LDL size, TG, and related atherogenic lipoproteins and candidate genes known to be involved in lipid metabolism. The linkage analysis was based on a sample of 126 DZ women twin pairs, which avoids the potentially confounding effects of both age and gender, by use of a quantitative sib-pair linkage-analysis approach. Eight candidate genes were examined, including those for microsomal TG-transfer protein (MTP), hepatic lipase, hormone-sensitive lipase, apolipoprotein (apo) B, apo CIII, apo E, insulin receptor, and LDL receptor. The analysis suggested genetic linkage between markers for the apo B gene and LDL size, plasma levels of TG, of HDL cholesterol, and of apo B, all features of the atherogenic lipoprotein phenotype. Furthermore, evidence for linkage was maintained when the analysis was limited to women with a major LDL-subclass diameter >255 A, indicating that the apo B gene may influence LDL heterogeneity in the intermediate-to-large size range. In addition, linkage was found between the MTP gene and TG, among all the women. These findings add to the growing evidence for genetic influences on the atherogenic lipoprotein phenotype and its role in genetic susceptibility to atherosclerosis.

Apolipoproteins B↗

PubMed1998

Evidence against linkage of familial combined hyperlipidemia to the apolipoprotein AI-CIII-AIV gene complex.

Familial combined hyperlipidemia (FCHL) was originally described as a disorder characterized by elevated levels of either plasma cholesterol or triglyceride (TG) or both in members ofthe same family. More recent studies have indicated that apolipoprotein B levels (apoB) are also elevated in these individuals. Although a dominant mode of inheritance was originally proposed, recent studies have questioned this simple mode of inheritance, and the genetic basis of the disorder has eluded investigators. A study that reported evidence that FCHL is linked to the apolipoprotein AI-CIII-AIV region on chromosome 11 is therefore of interest. We have attempted to replicate this finding in three large, well-characterized FCHL kindreds by using a highly polymorphic marker in the apoCIII gene. Using the same definitions and parameters as were used in the initial report, we obtained strong evidence against linkage of FCHL to the apolipoprotein AI-CIII-AIV region on chromosome 11 (combined lod score of -7.87 at 0% recombination). Two other models, one based on total cholesterol (TC) levels alone and one based on the joint distribution of TC and apoB levels, also gave evidence against linkage of FCHL to this region (lod scores at 0% recombination of -8.95 and -2.58, respectively). An additional regression-based linkage analysis also gave no support for the existence of a locus in this region that influences these lipid levels in these pedigrees. Explanations for the differences in results between these studies include genetic heterogeneity, differences in clinical phenotype used to select the pedigrees, and ascertainment bias.

Apolipoprotein A-I↗

PubMed1998

Plasma triglyceride as a risk factor for cardiovascular disease.

OBJECTIVES: To determine whether cardiovascular disease can be predicted from plasma triglyceride levels independent of high density lipoprotein (HDL) cholesterol levels. DATA SOURCES AND STUDY SELECTION: Seventeen prospective population-based studies, ranging in publication date from 1965 to 1994, were selected based on uniform criteria. Among the studies, 16 were conducted in men, comprising data for more than 46,000 men, with an average follow-up period of more than eight years. The data from women came from five studies, including nearly 11,000 women with an 11-year average follow-up. DATA EXTRACTION: The meta-analysis protocol comprised the following steps: estimating the relative risk of triglyceride for each individual study; standardizing the relative risks to a 1 mmol/l increase; estimating the variance and weighting relative risks by the inverse of the variance, and estimating the summary relative risk by averaging the weighted relative risks. DATA SYNTHESIS: Among studies of men, relative risks ranged from 1.1 to 2.0, and the summary relative risk was 1.32 (P < 0.05). All five studies of women were statistically significant, with relative risks ranging from 1.7 to 2.0. The summary relative risk was 1.76, higher than that for men, indicating a 76% increase in risk for women. For the studies among men in which HDL cholesterol data were available, multivariate adjusted relative risk was attenuated to 1.14 but was still statistically significant. Although only two studies of women included HDL cholesterol adjustments, the summary relative risk for triglyceride remained statistically significant, with a value of 1.37. CONCLUSIONS: When all available data are taken into account, increased triglyceride level is a risk factor for cardiovascular disease, independent of HDL cholesterol level. Clinical trials are urgently needed to determine whether lowering plasma triglyceride levels reduces subsequent risk of cardiovascular disease.

Cardiovascular Diseases↗

PubMed1997

Heritability of factors of the insulin resistance syndrome in women twins.

The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease (CHD) risk factors, including low high-density lipoprotein cholesterol (HDL-C) levels, obesity and increases in triglyceride (TG), blood pressure, small low-density lipoprotein particles (LDL), and both fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified 3 uncorrelated factors that explained 66% of the variance among these variables, based on data from women participating in examination 2 of the Kaiser Permanente Women Twins Study in Oakland, CA during 1989-1990. The factors were interpreted as: 1) body mass/fat distribution, 2) insulin/glucose, and 3) lipids: TG, HDL-C, LDL peak particle diameter. In this analysis, heritability of each of the factors was estimated based on data from 140 monozygotic and 96 dizygotic pairs of non-diabetic women twins. Heritability estimates were calculated using the classical approach, the analysis of variance (ANOVA) approach, and the maximum likelihood approach. For the body mass/fat distribution factor heritability estimates suggest moderate genetic influences; 0.61 (P < 0.001), 0.14 (P > 0.05), and 0.71 (P < 0.001), respectively. The insulin/glucose factor appeared to be highly heritable, with estimates of 0.87, 0.92, and 0.57 (all P < 0.001), respectively. The heritability estimates for the lipid factor were moderate and consistent across methods: 0.25 (P < 0.10), 0.32 (P < 0.05), and 0.30 (P < 0.05), respectively. These results are consistent with genetic influences on each of the 3 "factors," and suggest that both genetic and environmental effects are involved in the clustering of IRS risk factors.

Adolescent↗

PubMed1997

Genetic influences on changes in body mass index: a longitudinal analysis of women twins.

Numerous studies have demonstrated genetic influences on body fat, but there also may be genetic effects on its intraindividual variation over time. This study examined changes in body mass index (BMI) using longitudinal data from two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin pairs, with average ages of 41 years and 51 years at the two examinations, respectively. Age-adjusted heritability estimates for the change in BMI over the decade ranged from 0.57 to 0.86 (all p < or = 0.001) using three different statistical analysis approaches, indicating that at least half and possibly as much as 85%+, of the variance in the change in BMI is attributable to genetic influences under a polygenic model. These estimates remained statistically significant after adjusting for environmental factors (ranging from 0.57 to 0.78) and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79), although dizygotic intraclass correlations were low after these adjustments. Thus, in addition to known environmental and behavioral influences, these results provide evidence for genetic influences on changes in BMI over a decade in women.

Adolescent↗

PubMed1997

Triacylglycerol and coronary heart disease.

Based on meta-analysis of prospective studies from the epidemiological literature, TAG is a risk factor for CVD, independent of HDL-cholesterol. The RR values were 1.3 and 1.8 for a 1 mmol/l increase in TAG among men and women respectively. Adjustment for HDL-cholesterol and other risk factors attenuated these estimates, but they remained statistically significant. Recent prospective findings from the Stanford Five City Project (Gardner et al. 1996) and the Physicians' Health Study (Stampfer et al. 1996) further demonstrate that TAG and LDL size are highly inter-related risk factors for CHD. Quantitative genetic analysis from large-scale family studies show that these correlations reflect common genetic influences that may be important for understanding genetic susceptibility to CHD.

Coronary Disease↗

PubMed1997

Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: a longitudinal analysis.

We previously reported that change, with age, in plasma levels of total cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolipoprotein E (APOE) genotypes epsilon 3 epsilon 3 and epsilon 3 epsilon 4, in a sample of 77 older, unrelated males. By use of a larger sample from that cohort, followed longitudinally during 1969-87, the change in TC and in LDL-C, between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes, over three exams, was reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol (HDL-C), between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes-as well as the differences between the epsilon 3 epsilon 3 and epsilon 3 epsilon 2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams. At exam 1 TG was higher in the epsilon 3 epsilon 4 group than in the epsilon 3 epsilon 3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and 63 years, respectively) it was similar (P = .009 for the exam-by-genotype-interaction effect in the repeated-measures analysis). A similar trend was seen for TC (P = .03), yet previously detected LDL-C effects were not apparent (P = .46). Those with the epsilon 3 epsilon 2 genotype had higher TG and lower LDL-C and TC at each exam than were seen in those with the epsilon 3 epsilon 3 genotype, although the differences in the values were not always statistically significant. Differences in TC, LDL-C, and TG, between the epsilon 3 epsilon 2-genotype and epsilon 3 epsilon 3-genotype groups, did not significantly change over the three exams. HDL-C levels were relatively stable over the exams; however, the exam-by-genotype interaction was significant for the epsilon 3 epsilon 2 genotype versus the epsilon 3 epsilon 3 genotype (P = .02). The epsilon 4 allele effects on TG and TC changed between longitudinal exams and may be age dependent. Changes, with age, in the effect of the epsilon 3 epsilon 4 genotype on lipids may impact the risk of developing atherosclerotic disease.

Aged↗

PubMed1997

Heritability of longitudinal changes in coronary-heart-disease risk factors in women twins.

Numerous studies have demonstrated genetic influences on levels of coronary heart disease (CHD) risk factors, but there also may be genetic effects on the intraindividual variation in these risk factors over time. Changes in risk factors are likely to reflect genetic-environmental interactions and may have important implications for understanding CHD risk. The present study examines the heritability of changes in CHD risk factors, using data from the two examinations by the Kaiser Permanente Women Twins Study, performed a decade apart. The sample consisted of 348 pairs of women twins who participated in both examinations, including 203 MZ pairs and 145 DZ pairs. Average ages at the two examinations were 41 and 51 years, respectively. By means of three different statistical analytic approaches, moderate heritability estimates were demonstrated for changes in LDL cholesterol (h2 = .25-.36) and in HDL cholesterol (h2 = .23-.58), some of which were statistically significant. Although small to moderate heritability estimates were found for systolic blood pressure (.18-.37; P < .05 for some estimates), no genetic influence on changes in diastolic blood pressure was detected. Based on longitudinal twin data in women, this study demonstrates a genetic influence on changes in both lipoprotein risk factors and systolic blood pressure over a decade. In addition to environmental factors, which clearly are operating, the effect of various "variability genes" may be acting independently of the genetic influences on the absolute levels of these risk factors. Both mapping the gene(s) underlying intraindividual variations in these CHD risk factors and understanding their function(s) could lead to targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.

Adult↗

PubMed1997

A double-blind, randomized, controlled trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects taught the NCEP step I diet.

OBJECTIVE: We investigated the effect of egg feeding in 161 hypercholesterolemic (HC) or combined hyperlipidemic (CHL) free-living subjects taught the NCEP Step I Diet. METHODS: Subjects had LDL-C between 3.36 and 4.91 mmol/L (130 and 190 mg/dL). HC subjects had triglyceride concentrations < 75th %-ile, CHL > or = 75th %-ile. Six weeks after instituting the Step I Diet, subjects were randomized to two eggs or egg substitute daily for 12 weeks. RESULTS: Mean dietary intake (9-day food records) was within NCEP guidelines and 131 subjects finished with stable weight and adherence > 80%. Placebo group lipoprotein lipids were unchanged at study end for both HC (n = 35) and CHL (n = 21) subjects. Egg-fed HC subjects (n = 44) increased LDL-C nonsignificantly, 0.07 mmol/L (3 mg/dL) (p = 0.49). Egg-fed CHL subjects (n = 31) increased LDL-C 0.31 mmol/L (12 mg/dL) (p < 0.001). HDL-C increased significantly in both HC and CHL groups, 0.10 and 0.08 mmol/L (4 and 3 mg/dL, p = 0.003 and 0.02), respectively. HC and CHL subjects did not differ by apo E phenotype distribution. Postprandial triglyceride-rich lipoproteins and LDL subclass phenotype were unaffected by egg feeding in subsets of subjects. CONCLUSIONS: CHL subjects ingesting a Step I Diet in a free-living setting are sensitive to egg feeding and should benefit from dietary cholesterol restriction. The limited LDL-C rise in HC subjects resembles that seen in egg-fed normocholesterolemic subjects ingesting a Step I Diet, but requires confirmation.

Adult↗

PubMed1996

Guidelines of the National Heart, Lung, and Blood Institute Working Group on Blood Drawing, Processing, and Storage for Genetic Studies.

The guidelines presented here are intended for epidemiologic investigators who wish to store blood samples for genetic studies, either by extracting DNA directly from white blood cells or from immortalized cell lines. Recommended procedures for blood drawing and for processing samples are described. Protocols for freezing and storage of both white blood cells and extracted DNA are provided. Although the extraction of DNA and immortalization of cell lines should be conducted in collaboration with an experienced laboratory, a summary of the available methods with appropriate references is given, and a method for the extraction of DNA from clotted blood is referenced. In addition, criteria for selecting study subjects for whom immortalized cell lines are preferable to merely extracting DNA are presented. Finally, the use of alternative sources of genetic material, including cheek swabs and dried blood spots, is described briefly.

Blood Preservation↗

PubMed1996

Genetic and environmental influences on insulin levels and the insulin resistance syndrome: an analysis of women twins.

Multiple factors may determine insulin resistance and the insulin resistance syndrome. The contributions of genes and environment to the distribution of fasting insulin levels and to the associations of fasting insulin with elements of the syndrome were evaluated in the second examination of the Kaiser Permanente Women Twins Study (Oakland, California, 1989-1990). Subjects included 556 white women (165 monozygous twin pairs, 113 dizygous pairs; 455 women with normal glucose tolerance, 75 with impaired glucose tolerance, and 26 with non-insulin-dependent diabetes by World Health Organization criteria). The intraclass correlation coefficients for log fasting insulin for monozygous and dizygous twin pairs were 0.64 and 0.40, respectively. After adjustment for age, behavioral factors, and body mass index, the estimated classic heritability was 0.53 (p = 0.003). Commingling analysis of fasting insulin indicated the presence of four distributions (p < 0.001), consistent with at least one, and perhaps two, genes influencing this trait. In an unmatched multiple regression model among women from monozygous twin pairs only, log fasting insulin was independently associated with body mass index (p < 0.0001), waist/hip ratio (p = 0.02), and glucose intolerance (p = 0.04), but not with triglycerides, high density lipoprotein cholesterol, or hypertension. After removal of genetic influences by analysis of monozygous intrapair differences, only body mass index (p < 0.0001) remained independently related to fasting insulin. The authors conclude that, in addition to significant genetic influences on fasting insulin, environmental or behavioral factors (particularly nongenetic variation in obesity) are important determinants of fasting insulin and the insulin resistance syndrome.

Adult↗