Biomedical subjects

B D Mitchell

Publications and source records attributed to B D Mitchell.

At least 55 records · Page 3Linked to original sources

PubMed1997

Genetic relationship between measures of HDL phenotypes and insulin concentrations.

We used data from the San Antonio Family Heart Study to determine the HDL correlates of the insulin resistance syndrome (IRS), as reflected by insulin concentrations in nondiabetic subjects. We measured insulin concentrations both in the fasting state and 2 hours after a glucose challenge (2-hour insulin) and we assessed seven aspects of HDL phenotype, including size and concentration of both lipid and protein components. Measurements were obtained from 1202 nondiabetic members of 42 families. Initial quantitative genetic analyses revealed that a substantial portion of phenotypic variation in the nine variables was due to genes (heritabilities, h2, ranged from 0.32 to 0.47). We then conducted a series of bivariate genetic analyses, which indicated that there were significant additive genetic correlations (ie, pleiotropy) between the two measures of insulin and five of seven HDL measures tested, including concentrations of HDL cholesterol (fasting insulin only) and triglyceride, and HDL size distributions of apoAI, apoAII, and cholesterol; concentrations of apoAI and apoAII were not genetically related to either insulin measure. Increased insulin levels were associated with relatively smaller HDL phenotypes, and considering a similar association with small, dense LDLs, this finding suggests a common effect of insulin resistance on particle size distributions for these lipoproteins. Thus, these results suggest the existence of genes that pleiotropically influence variation in both HDLs and insulin levels and therefore contribute to the clustering of proatherogenic traits in the IRS.

Adult↗

PubMed1996

Effects of cigarette smoking, diabetes, high cholesterol, and hypertension on all-cause mortality and cardiovascular disease mortality in Mexican Americans. The San Antonio Heart Study.

Despite high levels of cardiovascular risk factors, Mexican Americans paradoxically have a lower prevalence of cardiovascular disease. A possible explanation is that conventional cardiovascular risk factors have a lesser impact on this ethnic group. In the present study, a 7- to 8-year follow-up of the San Antonio Heart Study cohort was used to estimate total and cardiovascular disease mortality and their association with baseline risk factors. A total of 2,629 Mexican Americans form the basis of this study, and 1,136 non-Hispanic whites from the same cohort served as the comparison group. The age- and sex-adjusted rates for total death and cardiovascular disease death were somewhat higher in Mexican Americans than non-Hispanic whites (rate ratio for total mortality = 1.4, 95% confidence interval 1.0-2.0; and rate ratio for cardiovascular mortality = 1.3, 95% confidence interval 0.7-2.4). After adjustment for sex, age, and socioeconomic status in multivariate analyses, current smoking, diabetes, high cholesterol, and hypertension were positively associated with all-cause mortality and cardiovascular disease mortality in Mexican Americans. Overall, these risk factors accounted for 45% of all-cause mortality and 55% of cardiovascular disease mortality in this ethnic group. In comparison, the risk factors accounted for 46% of all-cause mortality and 46% of cardiovascular disease mortality in non-Hispanic whites. The authors conclude that cigarette smoking, diabetes, high cholesterol, and hypertension are important predictors of both all-cause and cardiovascular disease deaths in Mexican Americans. There was no evidence for a diminished effect of these risk factors in Mexican Americans.

Adult↗

PubMed1996

Genetic and environmental contributions to cardiovascular risk factors in Mexican Americans. The San Antonio Family Heart Study.

BACKGROUND: The familial aggregation of coronary heart disease can be in large part accounted for by a clustering of cardiovascular disease risk factors. To elucidate the determinants of cardiovascular disease, many epidemiological studies have focused on the behavioral and lifestyle determinants of these risk factors, whereas others have examined whether specific candidate genes influence quantitative variation in these phenotypes. METHODS AND RESULTS: Among Mexican Americans from San Antonio (Tex), we quantified the relative contributions of both genetic and environmental influences to a large panel of cardiovascular risk factors, including serum levels of lipids, lipoproteins, glucose, hormones, adiposity, and blood pressure. Members of 42 extended families were studied, including 1236 first-, second-, and third-degree relatives of randomly ascertained probands and their spouses. In addition to the phenotypic assessments, information was obtained regarding usual dietary and physical activity patterns, medication use, smoking habits, alcohol consumption, and other lifestyle behaviors and medical factors. Maximum likelihood methods were used to partition the variance of each phenotype into components attributable to the measured covariates, additive genetic effects (heritability), household effects, and an unmeasured environmental residual. For the lipid and lipoprotein phenotypes, age, gender, and other environmental covariates accounted in general for < 15% of the total phenotypic variance, whereas genes accounted for 30% to 45% of the phenotypic variation. Similarly, genes accounted for 15% to 30% of the phenotypic variation in measures of glucose, hormones, adiposity, and blood pressure. CONCLUSIONS: These results highlight the importance of considering genetic factors in studies of risk factors for cardiovascular disease.

Adult↗

PubMed1996

Migration status, socioeconomic status, and mortality rates in Mexican Americans and non-Hispanic whites: the San Antonio Heart Study.

It has been claimed that Mexican Americans have a favorable mortality experience despite their low socioeconomic status (SES). The present study compared all-cause mortality of non-Hispanic whites with that of United States-born and foreign-born (i.e., born in Mexico) Mexican Americans. Subjects were 3735 residents of San Antonio, TX, who were followed-up for 7-8 years. The sex-age adjusted death rates per 1000 person-years were higher for United States-born Mexican Americans (5.7) than for non-Hispanic whites (3.8) or for foreign-born Mexican Americans (3.6). Foreign-born Mexican Americans had the lowest socioeconomic status (SES), and non-Hispanic whites had the highest SES. After adjustment for SES, the mortality ratio for United States-born Mexican Americans compared with foreign-born Mexican Americans was 1.9 (95% confidence interval, 1.0-3.5), while the ratio for United States-born Mexican Americans compared with non-Hispanic whites was 1.0 (95% confidence interval, 0.7-1.6). Stratified analysis revealed that those in the lowest SES tertiles had threefold greater risk of death than those in the highest tertiles among both United States-born Mexican Americans and non-Hispanic whites (test for trend, P < 0.001). These data suggest that lower SES is strongly associated with increased mortality. After adjustment for SES, mortality rates were similar for United States-born Mexican Americans and non-Hispanic whites. Foreign-born Mexican Americans had the lowest mortality rates of the three groups.

Adult↗

PubMed1996

Evidence for linkage of regions on chromosomes 6 and 11 to plasma glucose concentrations in Mexican Americans.

The genetic factors involved in type II diabetes are still unknown. To address this problem, we are creating a 10 to 15 cM genetic map on 444 individuals from 32 Mexican American families ascertained on a type II diabetic proband. Using highly polymorphic microsatellite markers and a multipoint variance components method, we found evidence for linkage of plasma glucose concentration 2 hr after oral glucose administration to two regions on chromosome 11: beta-hemoglobin (HBB) and markers D11S899/D11S1324 near the sulfonylurea receptor (SUR) gene. Iod scores at these two loci were 2.77 and 3.37, respectively. The SUR gene region accounted for 44.7% of the phenotypic variance. Evidence for linkage to fasting glucose concentration was also observed for two loci on chromosome 6, one of which is identical to a proposed susceptibility locus for type I diabetes (D6S290). When diabetics were excluded from the analyses, all Iod scores became zero, suggesting that the observed linkages were with the trait diabetes rather than with normal variation in glucose levels. Results were similar whether all diabetics were included in the analyses or only those who were not under treatment with oral antidiabetic agents or insulin.

Blood Glucose↗

PubMed1996

Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures.

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.

Adult↗

PubMed1996

Genetic and environmental correlations among hormone levels and measures of body fat accumulation and topography.

In this study we partition the phenotypic correlations between body fat measures and serum levels of hormones with known, or suspected, lipolytic effects into their genetic and environmental components. Using variance decomposition techniques, we are able to estimate the pleiotropic effects of genes and/or shared environmental factors that give rise to the phenotypic correlations previously reported between these traits. We used data from a large sample of randomly ascertained Mexican-American families living in San Antonio, TX. Data were available for 582 individuals in 26 pedigrees. Levels of sex hormone-binding globulin, dehydroepiandrosterone sulfate, insulin, insulin-like growth factor I, total T4, and total T3 were assayed. The measures of body fat accumulation and topography included body mass index, subscapular/triceps ratio, and relative fat patterning index. The results of this analysis demonstrate that significant phenotypic correlations among these traits can arise from three underlying conditions: 1) entirely from shared genetic effects (pleiotropy), 2) entirely from shared random environmental effects, or 3) a combination of both effects. However, we also show that it is possible for significant genetic and environmental correlations to interact in such a way as to produce a phenotypic correlation that itself would not be considered significant.

Adipose Tissue↗

PubMed1996

Evidence for a major gene for type II diabetes and linkage analyses with selected candidate genes in Mexican-Americans.

We have carried out two independent family studies in low-income Mexican-Americans from San Antonio, Texas. In the first study, probands were ascertained at random without regard to any medical condition (658 examined individuals from 50 families), and in the second study, probands were subjects with type II diabetes identified in a prior epidemiological survey (523 examined individuals from 29 families). Pedigrees ranging in size from 2 to 45 family members (median 11) in the first study and from 2 to 50 family members (median 12) in the second study were examined. Diabetes was diagnosed according to World Health Organization criteria. In both sets of families, segregation analyses revealed support for a major gene with an autosomal dominant mode of inheritance influencing early age of onset of diabetes. Non-Mendelian inheritance was rejected in both data sets. Individuals with the early age of onset allele had a mean age of diabetes onset of 51 years in the first data set and 60 years in the second data set. In the first data set, the major gene accounted for approximately 70% of the phenotypic variance in age of onset of diabetes, and there were no residual family effects once the major gene effect was taken into account. In the second data set, the major gene accounted for approximately 50% of the phenotypic variance, and residual family effects were statistically significant. Linkage analyses were performed with 11 candidate genes, and tight linkage with diabetes was rejected for Rh blood group, glucose transporter 2, fatty acid-binding protein, tumor necrosis factor beta, glucokinase, and lipoprotein lipase. A logarithm of odds (LOD) score of 0.92 at a recombination fraction of 0.05 was observed for insulin receptor substrate 1. This LOD score corresponds to a chi2 of 4.24 (P = 0.039).

Alleles↗

PubMed1996

Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7.

Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and approximately 73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is approximately 15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans.

Adult↗

PubMed1995

Major gene with sex-specific effects influences fat mass in Mexican Americans.

Increased adiposity has repeatedly been identified as a major risk factor for a variety of chronic diseases. However, the question still remains whether the amount of adipose tissue itself is genetically mediated. To address this question, a segregation analysis, using maximum likelihood techniques as implemented in the computer program Pedigree Analysis Package (PAP), was performed on fat mass (kilograms of body fat) in a large sample of extended Mexican American families residing in San Antonio, TX. The only model not rejected was a Mendelian mixed model for fat mass, incorporating genotype x sex interaction. In males the major gene accounted for 37% of the total variance compared with 43% in females. In both sexes homozygous recessive individuals have a fat mass more than double that of individuals of the other two genotypes. It was possible to reject linkage of the anonymous major gene for fat mass with several candidate loci for obesity. However, tentative evidence of linkage was detected with markers on both chromosomes 2 and 11, thereby providing hypotheses for future testing.

Adolescent↗

PubMed1995

Segregation and linkage analysis of the complex trait Q1.

Segregation and linkage analysis of GAW9 Problem 2 quantitative trait 1 (Q1) was performed. Eight segregation models comprising all possible combinations of the environmental factor (EF), quantitative trait 2 (Q2), and quantitative trait 3 (Q3) as covariates were considered. Seven of the eight segregation models showed strong evidence for a major gene, the other model was marginal. When all genotypes are known, some evidence for linkage (lod > 2) was found to all three of the markers that affect Q1. Furthermore, four of the eight models each showed some linkage (lod > 2) to two of the three markers that affect Q1 with no false positives. Each of these segregation analysis major genes is a hybrid combination of the true multiple loci that affect Q1.

Alleles↗

PubMed1995

The influence of response bias on segregation and linkage analysis.

Response bias in epidemiologic studies can occur if affected individuals are more (or less) likely to participate in a survey than their unaffected counterparts. To examine the effect of response bias in the context of a family study, we conducted segregation and linkage analysis in all 1,000 individuals in the Problem 2 data set, and in two different 65% samples: one sample consisting of 648 randomly selected individuals, and the other sample nonrandomly constructed so that individuals with high levels of Q1 were oversampled. In this simulation the ability to detect major genes for Q1-Q4 in segregation analysis and to link these putative major genes to genetic markers in linkage analysis was not markedly different between the 65% random and the 65% enriched samples.

Alleles↗

PubMed1995

Differential impact of obesity in related populations.

To search for genetic and environmental determinants of obesity, we compared the prevalences and the impact of obesity in three populations from two cities: Mexican Americans (n = 820) and non-Hispanic whites (n = 1112) from San Antonio, Texas, and Mexicans from Mexico City (n = 1878). In the age range examined, 35-64 years, only Mexican men and women showed a significant increase in the prevalence of obesity with age. On the other hand, genetic ancestry, especially in women, made significant differences in the rates of obesity. Mexican Americans showed relatively high, and non-Hispanic whites low, rates of obesity. To discriminate between genetic and environmental influences mediating the impact of obesity on a set of hemodynamic and metabolic variables, we compared this impact between Mexican Americans and both non-Hispanic whites (same macro-environment, different gene pools), and Mexicans (same gene pool, different environments). We found that obesity always worsens the hemodynamic and metabolic profiles of individuals, but the magnitude of the effects may be variable. We showed that the levels of insulin concentrations for a given level of obesity were similar in Mexicans and Mexican Americans, suggesting that genetic influences predominate in determining insulin levels; the levels of triglycerides and HDL for a given level of obesity were similar in Mexican Americans and non-Hispanic whites, suggesting predominant environmental influences on lipid levels. On the other hand, the levels of glucose and systolic blood pressure for a given level of obesity were usually different between Mexican Americans and either of the other two populations, suggesting that these levels may result from genotype-by-environment interactions.

Adult↗

PubMed1995

Is there an excess in maternal transmission of NIDDM?

Family studies have demonstrated that there is a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), although the mode of inheritance is unknown. A number of recent family history studies, including one in Mexican Americans, have suggested that there is an excess of maternal transmission of NIDDM. Family history studies are subject to various types of bias, however, and the potential for bias in many of these studies has not been thoroughly evaluated. We therefore tested the hypothesis that diabetes is more likely to be transmitted from mothers than from fathers using data collected from a large family study of low-income Mexican Americans in San Antonio, Texas. The parents and offspring from 318 different nuclear families attended our medical clinic, where they received a 2-h oral glucose test. Diabetes was diagnosed on the basis of World Health Organization criteria. The sibships were classified into diabetic sibships (at least one sibling in the sibship was diabetic; n = 54) and non-diabetic siblings (no diabetic siblings; n = 264). The prevalence of diabetes among mothers of diabetic siblings was 61.4% (27 of 44) compared to 64.3% (18 of 28) among fathers of diabetic siblings (rate ratio = 0.95; 95% confidence interval; 0.51-1.84). For the non-diabetic sibships, the prevalence of diabetes was 31.7% (78 of 246) and 28.9% (37 of 128) among mothers and fathers, respectively (rate ratio = 1.09; 95% confidence interval: 0.73-1.67). These data provide no evidence for an excess maternal transmission of diabetes in Mexican Americans.

Age of Onset↗

PubMed1995

Accuracy of anticardiolipin antibodies in identifying a history of thrombosis among patients with systemic lupus erythematosus.

OBJECTIVE: To measure the accuracy of anticardiolipin antibodies (aCL) in identifying a history of thrombosis among patients with systemic lupus erythematosus (SLE) or the primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS: Patients with SLE or PAPS who attended our rheumatology clinic between April 1992 and March 1994 were included in a retrospective analysis of the relationship between thrombotic events and aCL. All aCL measurements were performed in the same laboratory by enzyme-linked immunosorbent assay, blinded as to the presence or absence of thrombosis. The diagnostic accuracy of IgG, IgM, and IgA aCL was quantified by means of the receiver operating characteristic area under the curve (ROC AUC) for each isotype. Stratum-specific likelihood ratios and their 95% confidence intervals were calculated to define strata with optimal discriminant power. RESULTS: During the period of study, aCL was measured in 117 patients (113 SLE and 4 PAPS), of whom 24 (20.5%) had experienced thrombotic events. The ROC AUC +/- the standard error for IgG aCL was 0.81 +/- 0.05, signifying an 81% accuracy in the identification of a history of thrombosis. In contrast, the accuracy of the IgM and IgA aCL was significantly lower (0.60 +/- 0.08 and 0.54 +/- 0.07, respectively, P < 0.05). Using stratum-specific likelihood ratios, we defined three strata in the IgG aCL scale that discriminate between patients with low, indeterminate, and high probabilities of thrombosis. For IgG aCL levels below 21.4 IgG phospholipid (GPL) U/mL, the posttest probability of thrombosis was 0.07, whereas for IgG aCL levels > or = 65.1 GPL U/mL, the posttest probability of thrombosis was 0.75. For IgG aCL values between 21.4 and 65.0 GPL U/mL, the probability of thrombosis was 0.20, equivalent to the entire cohort. CONCLUSIONS: The IgG aCL determinations perform well in the identification of thrombosis in SLE or PAPS, while the IgM and IgA aCL have poor diagnostic accuracy. These findings may have implications for management of these patients.

Adolescent↗

PubMed1995

Myocardial infarction and cardiovascular risk factors in Mexico City and San Antonio, Texas.

Because the epidemiology of cardiovascular disease in Mexico is largely unknown, we examined the prevalence of cardiovascular risk factors and myocardial infarction (MI) in adults from low-income colonias in Mexico City. Data were collected as part of the Mexico City Diabetes Study, a population-based survey of diabetes and cardiovascular disease conducted between 1987 and 1992. Results were compared with those obtained from a comparable survey conducted previously among low-income Mexican Americans in San Antonio, Tex. A total of 2271 individuals between the ages of 35 and 64 years from Mexico City and 1143 adults of the same age range from San Antonio were studied. Despite being leaner and having lower levels of total cholesterol, Mexicans in Mexico City had markedly higher levels of triglycerides (P < .001) and lower levels of HDL cholesterol (P < .001) than Mexican Americans in San Antonio. MI was assessed by Minnesota-coded electrocardiograms and by a self-reported history of physician-diagnosed heart attack. In men, the prevalence of self-reported heart attack was significantly higher in San Antonio than in Mexico City (odds ratio, 5.85; P < .001), and in women, the prevalence of electrocardiogram-documented MI was significantly higher in San Antonio than Mexico City (odds ratio, 2.51; P < .001). The apparent excess of MI in San Antonio relative to Mexico City could be due to higher case-fatality in Mexico City or to a higher incidence in San Antonio.

Adult↗

PubMed1995

Evidence for a major gene affecting postchallenge insulin levels in Mexican-Americans.

Hyperinsulinemia, which is considered a hallmark of insulin resistance, precedes the development of non-insulin-dependent diabetes mellitus (NIDDM). Results of family and twin studies have shown that heredity influences insulin resistance and insulin levels. In Caucasian families ascertained through two or more NIDDM siblings, it has been reported that single genes with large effects, i.e., major genes, influence both fasting and 1-h postchallenge insulin levels. To determine whether a major gene affects 2-h postchallenge insulin levels in Mexican-Americans, we conducted segregation analyses using data collected on 527 pedigreed individuals from 27 families in San Antonio, TX. Probands for the families were randomly ascertained and all first-, second-, and third-degree relatives aged 16 years and older were invited to participate. Subjects received a 2-h oral glucose tolerance test, and diabetes was diagnosed according to World Health Organization criteria. We found that an autosomal dominant major gene best described the inheritance of 2-h insulin levels (ln-transformed) in these 27 families. Of the individuals in the population, 17% were homozygous for the 2-h low-insulin allele (back-transformed mean = 125 pmol/l) and 83% were heterozygous or homozygous for the 2-h high-insulin allele (back-transformed mean = 406 pmol/l). This major gene accounted for 31% of the variance in ln(2-h insulin levels) in this population. Using quantitative trait linkage analyses, we excluded tight linkage between this gene affecting 2-h insulin levels and three candidate loci for insulin levels: the insulin receptor gene, the low-density lipoprotein receptor gene, and the glucokinase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Evidence for linkage of postchallenge insulin levels with intestinal fatty acid-binding protein (FABP2) in Mexican-Americans.

Single genes with large effects may contribute to insulin resistance or influence susceptibility to non-insulin-dependent diabetes mellitus (NIDDM). In the Pima Indians, results from sib-pair analysis have suggested that a gene on chromosome 4q influences both fasting insulin levels and maximal insulin action. We conducted sib-pair and logarithm of odds (LOD)-score linkage analysis to seek evidence for linkage between genes influencing insulin levels and chromosome 4q loci. Analyses were conducted on nondiabetic individuals from 28 different families participating in the San Antonio Family Diabetes Study. All subjects received a 2-h oral glucose tolerance test. Fasting insulin levels were measured in 382 nondiabetic individuals, and 2-h insulin levels were measured in 366 individuals. Initial sib-pair linkage analysis revealed a possible association between 2-h post-glucose challenge insulin levels and the intestinal fatty acid-binding protein (FABP2) locus located in the region of chromosome 4q28-31 (P = 0.006). Subsequent sib-pair linkage analysis of 11 additional chromosome 4q markers supported this hypothesis. We next conducted segregation analyses to estimate allele frequencies and other model parameters for the putative locus influencing 2-h insulin levels. Results of LOD-score linkage analysis indicated possible linkage between the major gene described by the segregation model and FABP2. Using combined segregation and linkage analysis, we obtained a LOD-score of 2.80 at recombination frequency of 0.0 between FABP2 and the putative locus influencing 2-h insulin levels. The maximum likelihood estimate of the allele associated with low insulin levels was 0.21.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗