Biomedical subjects

J E Eichner

Publications and source records attributed to J E Eichner.

11 recordsLinked to original sources

PubMed1992

Genetic variation in two bone-related proteins: is there an association with bone mineral density or skeletal size in postmenopausal women?

In an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non-Black women (age 65-90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone-related proteins, group specific component (Gc), also known as vitamin D-binding protein, and alpha 2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P less than .02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding.

Aged↗

PubMed1992

The impact of the apolipoprotein E polymorphism on the lipoprotein profile in insulin-dependent diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study IX.

The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.

Adult↗

PubMed1991

The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial.

The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation.

Adult↗

PubMed1991

A simplified method for screening the apolipoprotein E polymorphism.

A simple method for screening populations for the apolipoprotein E polymorphism which involves isoelectric focusing of delipidated samples on polyacrylamide gels of pH 4.5-5.8 followed by immunoblotting using a double-antibody technique is presented. The method is a synthesis of two previously published procedures and works well on samples that have been stored for as long as 15 years.

Adult↗

PubMed1990

Alpha 2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women.

It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha 2-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white postmenopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P = 0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.

Aged↗

PubMed1989

Phenotypic effects of apolipoprotein structural variation on lipid profiles. I. APO H and quantitative lipid measures in the healthy women study.

Apolipoprotein H (APO H), also known as beta 2-glycoprotein I, has been identified as a protein component of the major lipoprotein density fractions in human plasma. Recently, genetically determined structural polymorphism in white and black populations has been documented for this apolipoprotein. There are three common alleles in whites and blacks and a fourth allele found mainly in blacks. Family data confirm the autosomal codominant pattern of inheritance for the APO H structural gene. Little is known about the function of APO H, but it has demonstrated both lipid and platelet involvement. In this study we investigate the effect of APO H phenotypes on quantitative lipid measures in a group of 443 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. None of the APO H phenotypes showed a statistically significant effect on lipid measures in this population.

Adult↗

PubMed1989

Phenotypic effects of apolipoprotein structural variation on lipid profiles: II. Apolipoprotein A-IV and quantitative lipid measures in the healthy women study.

Apolipoprotein A-IV (APO A-IV) is a major protein component of mesenteric lymph chylomicrons and very-low-density lipoproteins. It is found in plasma predominantly unassociated with major lipoprotein fractions and in high density lipoproteins. APO A-IV exhibits structural heterogeneity owing to two codominant alleles, APO A-IV*1 and APO A-IV*2, that occur in Caucasian and black populations. In vitro experimental evidence indicates that APO A-IV may be a cofactor for the lecithin:cholesterol acyltransferase enzyme, may be involved in reverse cholesterol transport, and may play an important role in the modulation of lipoprotein lipase activity. In this study we have investigated the effect of two APO A-IV phenotypes, APO A-IV 1-1 and APO A-IV 2-1, on quantitative lipid measures in a group of 453 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. Of the nine lipid measures, triglycerides showed a marginally significant effect caused by phenotype. The APO A-IV 2-1 heterozygotes had lower average triglycerides than the 1-1 homozygotes (P = .053).

Adult↗

PubMed1989

Phenotypic effects of apolipoprotein structural variation on lipid profiles. IV. Apolipoprotein polymorphisms in a small group of black women from the healthy women study.

Structural variation in apolipoprotein E has been shown to influence lipid and lipoprotein concentrations. The purpose of the present study was to investigate several apolipoproteins in a group of Black women from the Healthy Women Study (HWS). HWS is a community-based prospective study of 541 premenopausal women who are being followed through the menopause to determine the influence of biological, genetic, and psychosocial phenomenon on cardiovascular risk factors. Of the 541 subjects, 48 are Black. Serum from most of these 48 Black women was used to type seven apolipoproteins (APO A-I, APO A-II, APO A-IV, APO C-II, APO D, APO E, and APO H). Five of these apolipoproteins are polymorphic in Blacks (APO A-IV, APO C-II, APO D, APO E and APO H). Only two and three individuals, respectively, were heterozygous at the APO D and APO C-II loci. APO A-IV, E, and H exhibited more variation, however, only APO E phenotypes could be used for statistical analyses. Three common phenotypes, APO E 3-2, APO E 3-3, and APO E 4-3, were used in analysis of variance on four quantitative lipid variables. Despite small numbers, the effect of APO E phenotype was apparent. The APO E 3-2 phenotype showed reduced average levels of total cholesterol, apolipoprotein B (APO B) and low-density lipoprotein cholesterol (LDLc), and the APO E 4-3 phenotype showed increased levels (P less than or equal to .0497). The APO E3-3 homozygote was intermediate on all three. Because of small numbers in the cells of APO A-IV and APO H phenotypes, these were not analyzed with respect to quantitative lipids.

Adult↗

PubMed1989

Genetic studies of low-abundance human plasma proteins. XII. A new variant of corticosteroid-binding globulin detected by isoelectric focusing/immunoblotting.

Thin-layer polyacrylamide gel isoelectric focusing over the pH range 3.5-5 followed by immunoblotting was used to investigate the occurrence and frequency of genetic variation in corticosteroid-binding globulin (CBG). Plasma samples from US Caucasians (n = 105) and US Blacks (n = 106) from Pittsburgh, Pa., Canadian Indians from Vancouver Island (n = 91) and Nigerian Blacks (n = 116) were analyzed. A complex isoprotein pattern was observed in all individuals tested. Reduction of this pattern to a single primary band following neuraminidase treatment indicates that the observed intraindividual variation is due to variation in the number of sialic acid residues associated with CBG. The CBG variant pattern consisted of a series of isoprotein bands having the same mobility as the common pattern, and a second series of bands at a more acidic isoelectric point. This pattern is consistent with heterozygosity for a rare CBG allele.

Blood Proteins↗

PubMed1987

Von Recklinghausen neurofibromatosis: a linkage study of candidate and random marker genes.

Genotyping, using plasma proteins or DNA polymorphisms or both, was carried out on 30 families selected through probands with Von Recklinghausen disease. The data provide additional evidence for the exclusion of loci on chromosomes 3 and 5, and chromosome arms 1q, 2p, 4p, 4q, 6q, 7p, 9q, 11p, 11q, and 14q. There was no evidence for genetic heterogeneity at D1S1 (DNF15S2) on chromosome arm 3p, using the Morton test for heterogeneity.

Blood Proteins↗

PubMedDate not supplied

Phenotypic effects of apolipoprotein structural variation on lipid profiles. III. Contribution of apolipoprotein E phenotype to prediction of total cholesterol, apolipoprotein B, and low density lipoprotein cholesterol in the healthy women study.

The apolipoprotein (apo) E structural locus has been shown to influence concentrations of total cholesterol, apo B, and low density lipoprotein (LDL) cholesterol in population studies. Apo E has six phenotypes resulting from three common alleles at this locus. In the present study, we have typed 473 healthy white women for apo E. At baseline in 1984, all women were premenopausal. To date, 109 of these women have become postmenopausal and are not on hormone therapy. Statistical analyses were done on both pre- and postmenopausal groups to assess the influence of menopausal status in combination with the apo E locus on lipid profile. Nine lipoprotein lipids and apolipoproteins were categorized by three apo E phenotypes: apo E3-2, apo E3-3, and apo E4-3. These were compared in analysis of variance. At baseline, the apo E3-2 phenotype showed the lowest average concentrations of total cholesterol (170 mg/dl), apo B (80 mg/dl), and LDL cholesterol (91 mg/dl), while the apo E4-3 phenotype demonstrated the highest average concentrations of total cholesterol (192 mg/dl), apo B (104 mg/dl), and LDL cholesterol (116 mg/dl) (p less than or equal to 0.0004). Apo E3-3 homozygotes were intermediate on all three quantitative variables. The postmenopausal subset showed the same trends by phenotype, with overall increases in total cholesterol, apo B, LDL cholesterol, and triglycerides, regardless of phenotype. Women who remained premenopausal generally showed smaller increases in these same measures. Our results suggest that, on average, the lower lipoprotein values for the apo E3-2 phenotype are maintained through early menopause despite a worsening of lipid profiles for all women as they age.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗