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Biomedical subjects

R C Go

Publications and source records attributed to R C Go.

At least 37 records · Page 2Linked to original sources
PubMed1997

ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative.

OBJECTIVE: To explore the impact of apoE-4 on Alzheimer's disease (AD) and its age at onset. DESIGN: A genetic linkage study using affected relative pairs, predominantly siblings. SETTING: Three academic medical centers ascertained subjects from memory disorder clinics, nursing homes, and the local community. SUBJECTS: 310 families including 679 subjects with AD by NINCDS/ADRDA and/or Khachaturian criteria and 231 unaffected subjects. OUTCOME MEASURE: ApoE genotype. ANALYTIC METHODS: Association, affected pedigree member, sibling pair, and lod score analyses. RESULTS: ApoE-4 was strongly associated with AD in this sample (allele frequency = 0.46 vs. 0.14 in controls, p < 0.000001). Results of lod score, affected pedigree member analysis, and sib-pair analysis also supported apoE-4 as a risk factor for AD. When the sample was stratified on family mean age at onset, the risk conferred by apoE-4 was most marked in the 61 to 65 age group. Individuals with two copies of apoE-4 had a significantly lower age at onset than those with one or no copies (66.4 vs. 72.0, p < 0.001), but individuals with one copy did not differ from those with none. Within families, the individual with the earliest age at onset had, on average, significantly more apoE-4 alleles (p < 0.0001) than the individual with the latest onset. DISCUSSION: This work supports previous reports of an association between apoE-4 and the development of AD and demonstrates that apoE-4 exerts its maximal effect before age 70. These findings have important implications for the potential use of apoE genotyping for diagnosis and prediction of disease. They also underscore the need to identify additional genetic factors involved in AD with onset beyond age 70 years.

Age of Onset↗
PubMed1996

Genetic epidemiologic methods to screen for matrilineal inheritance in mitochondrial disorders.

We propose a method to screen for the matrilineal inheritance in mitochondrial disorders by comparing the risk of disease in a person whose mother is affected or whose maternal grandmother or aunt or uncle is affected to the risk of disease in a person whose father is affected or whose paternal grandmother or aunt or uncle is affected using a modification of the reconstructed cohort design. Sampling of pedigrees is accomplished via probands and must not be influenced by family history. The cohort of the proband's offspring, and offspring of the proband's siblings, can be analyzed using survival analysis. Cox proportional hazards model, Bonney's [(1986) Biometrics 42:611-625] model, and Liang's [(1991) Genet Epidemiol 8:329-338] model. Mitochondrial transmission can be distinguished from X-linked transmission by examining sex-specific patterns of disease expression in matrilineally transmitted diseases. To illustrate our epidemiologic method, we apply our screening method to pedigrees of two disorders which have been proposed to have a mitochondrial DNA component to their inheritance.

Bipolar Disorder↗
PubMed1995

SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer's disease family.

Alzheimer's disease (AD) is a progressive, degenerative neurological disorder of the central nervous system. AD is the fourth leading cause of death in elderly persons 65 years or older in Western industrialized societies. The etiology of AD is unknown, but clinical, pathological, epidemiological, and molecular investigations suggest it is etiologically heterogeneous. Mutations in the amyloid protein are rare and segregate with the disease in a few early-onset familial AD (FAD) families. Similarities between AD and the unconventional viral (UCV) diseases, and between the amyloid and prion proteins, implicate the human prion protein gene (PRNP) as another candidate gene. Single strand conformation polymorphism (SSCP) analysis was used to screen for mutations at this locus in 82 AD patients from 54 families (30 FAD), vs. 39 age-matched controls. A 24-bp deletion around codon 68 that codes for one of five Gly-Pro rich octarepeats was identified in two affected sibs and one offspring of one late-onset FAD family. Two other affected sibs, three unaffected sibs, and three offspring from this family, in addition to one sporadic AD patient and three age-matched controls, were heterozygous for another octarepeat deletion located around codon 82. Two of the four affected sibs had features of PD, including one who was autopsy-verified AD and PD. Although these deletions were found infrequently in other AD patients and controls, they appear to be a rare polymorphism that is segregating in this FAD family. It does not appear that mutations at the PRNP locus are frequently associated with AD in this population.

Alzheimer Disease↗
PubMed1994

Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative.

OBJECTIVE: To assess interrater reliability and validity of NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer's disease (AD). DESIGN: A multisite reliability and validity study in which clinicians from each site diagnosed 60 case summaries yielding a preconsensus estimate of reliability and validity. A consensus conference was conducted for each disagreement, leading to a postconsensus estimate of validity. The criterion standard was a diagnosis of AD by autopsy. SETTING: Three academic medical centers. SUBJECTS: A convenience sample of 60 detailed case summaries, 40 with AD and 20 with other dementing disorders. MAIN OUTCOME MEASURES: The kappa coefficient, sensitivity, and specificity. RESULTS: The kappa coefficient for preconsensus agreement on a diagnosis of probable or possible AD vs non-AD was 0.51; the sensitivity of a diagnosis of probable or possible AD for a pathological diagnosis of AD was 0.81, and the specificity was 0.73. The postconsensus sensitivity was 0.83, and the specificity was 0.84. CONCLUSIONS: The results support the reliability and validity of NINCDS-ADRDA criteria and show that the consensus process may improve diagnostic accuracy. The cases are reviewed with a focus on the sources of diagnostic disagreements and errors and possible changes that might improve the accuracy of the criteria.

Aged↗
PubMed1994

Glucokinase gene in gestational diabetes mellitus: population association study and molecular scanning.

Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of the mutant glucokinase kindreds were originally diagnosed as having gestational diabetes. This study examined the glucokinase gene in 270 American Black women, including 94 with gestational diabetes whose diabetes resolved after pregnancy (gestational diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after pregnancy (overt diabetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking either end of the glucokinase gene were evaluated. No association was found between glucokinase alleles and gestational diabetes only or overt diabetes, after adjustment for multiple comparisons. To detect single base changes, all 11 exons and proximal islet and liver promoter regions were examined by polymerase chain reaction plus single-stranded conformational polymorphism analysis in 45 gestational diabetes only patients who had not yet developed Type 2 diabetes. Nine coding region variants were identified: Ala11 (GCC) to Thr11 (ACC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in splicing consensus sequences. Analysis of the promoter regions revealed two common variants, G-->A at islet -30 (24%), and G-->A at liver -258 (42%). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, but did not differ among the three groups. Thus, no significant coding sequence glucokinase mutations were found in 90 alleles from 45 patients with gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

HLA in ankylosing spondylitis: is HLA-B27 the only MHC gene involved in disease pathogenesis?

Linkage analysis of HLA haplotypes, HLA-B27 subtypes, and a 9.2-kb PvuII B7 restriction fragment length polymorphism (RFLP) (shown previously to be associated with peripheral arthritis in ankylosing spondylitis [AS]) in 115 relatives from 12 multiplex spondyloarthropathy (SNSA) and 2 B27-positive control families showed AS to be linked to HLA-B27 haplotypes. The RFLP segregated with HLA-A3- and HLA-A9-bearing haplotypes (lod score, 10.98; odds in favor of linkage, 9.2 x 10(10):1), although its linkage to AS or other SNSA per se was not seen. The association of HLA-A3/A9 with the RFLP was also seen in 52 AS patients and 92 controls, although no HLA-A, -B, -C, or -DR allele (other than HLA-B27) was significantly increased in frequency. The HLA-B27 subtype seen on all but one of the haplotypes studied was B*2705, the sole exception being HLA-B*2702. Although not ruling out a second HLA-A-linked gene influencing the clinical expression of AS, these data fail to support the role of a second MHC-associated gene in the pathogenesis of AS per se.

Alleles↗
PubMed1994

Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

Adult↗
PubMed1994

Genes within the major histocompatibility complex predict NIDDM in African-American women in Alabama.

OBJECTIVE: To test the hypothesis that genes within the major histocompatibility complex (MHC) are associated with gestational diabetes mellitus (GDM) and, subsequently, non-insulin-dependent diabetes mellitus (NIDDM) in African-American women. RESEARCH DESIGN AND METHODS: African-American women who presented with GDM were compared with pregnant African-American control subjects. Following pregnancy, GDM patients were assessed at various intervals of time (median = 6 years) to determine whether they had developed diabetes. RESULTS: GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects. GDM patients who subsequently developed NIDDM had a significantly higher frequency of B41, DR2, and BF-S and a lower frequency of DR1 and DR6 phenotypes than control subjects. Even after controlling for age and body mass index, B41 and DR2 were independent predictors of developing insulin-requiring GDM and NIDDM in GDM subjects. CONCLUSIONS: These results suggest that either one or more genes within the MHC are involved in the etiology of NIDDM.

Alabama↗
PubMed1992

Sexual differences in lipoprotein composition in a family with dyslipidemic hypertension with premature atheroschlerosis: deficiency of high-density lipoprotein-L and high-density lipoprotein-M "apolipoprotein-I alone" particle.

This article describes a family with a high incidence of premature atherosclerosis and primary hypertriglyceridemia in the women. The lipoprotein composition of this family was investigated with a new methodology that combines gradient ultracentrifugation to isolate lipoprotein subfractions with high-performance liquid chromatography to quantitate apolipoproteins. The major lipoprotein abnormalities that were identified in the hyperlipidemic women in this family were (1) an increased mass of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) with triglyceriderich VLDL but normal IDL composition; (2) triglyceride-rich low-density lipoprotein (LDL) with normal cholesterol and apolipoprotein B concentrations; (3) a relatively normal total mass of high-density lipoprotein (HDL)-L and HDL-M but with a reduction in the apolipoprotein A-I/A-II ratio and a decrease in the cholesterol to triglyceride ratio; (4) an elevation of HDL-D apolipoprotein A-I. The reduction in the apolipoprotein A-I/A-II ratio was also seen in the hyperlipidemic men and in most of nonhyperlipidemic family members and was the most common lipoprotein abnormality that was identified in this family (9 of 11 family members who were not on lipid-lowering medications were affected). The hypertriglyceridemic women appeared to have an increase in the "A-I + A-II" HDL particles in all subfractions and an increase in the "A-I alone" particles in HDL-D. These increases provided the apparently normal total mass of HDL that was observed in these women. These increases in HDL were not seen in the hypertriglyceridemic men. We conclude that a deficiency of the "A-I alone" particle in HDL-L and HDL-M may contribute to the premature atherosclerosis that was seen in this family and that it appears to precede the appearance of hypertriglyceridemia. The increase in the "A-I + A-II" HDL particles did not appear to provide the same protection as would be expected from "A-I alone" HDL.

Adult↗
PubMed1991

Gestational diabetes mellitus among African-American women.

Gestational diabetes mellitus (GDM) is associated with increased risk of poor outcomes for the pregnancy. It is a strong risk factor for subsequent diabetes. The epidemiology of GDM in African-American women is not well known. It has not been demonstrated that their risk factors are similar in character and weight to those among White women. There is considerable multicollinearity among GDM risk factors such as age, parity, obesity, hypertension, and family history of diabetes, and this needs to be sorted out. This review is based on the results of a nested case-control study to evaluate the frequency of, and the relationships of the known risk factors with, the onset of GDM among African-American women. All cases of GDM within a cohort of women seen at any of the county health department clinics in Jefferson County, Alabama from 1981 to 1987 were identified. The cohort represents approximately 63% of all African-American pregnancies in the county during the period. With few exceptions (5.1% based on fasting plasma glucose greater than or equal to 120 mg/dl), potential GDM cases (7.1%) were selected on the basis of a 2 h post 100 g carbohydrate meal screening plasma glucose measure at their second prenatal visit and again at 28-32 weeks greater than or equal to 115 mg/dl and diagnosed on the basis of the results of an oral glucose tolerance test (OGTT) using the criteria of O'Sullivan and Mahan. Women with any prior history of diabetes (even in pregnancy), 1.6%, were excluded. The frequency of the new diagnosis of GDM among African-American women in this pregnancy in the cohort was 2.5% of pregnancies and 3.4% of women, which is similar to the values reported in the other studies. Controls were selected from women with negative screening tests who delivered after a GDM subject. The results reported in this paper reflect 358 cases (86% of all eligible GDM cases identified) and 273 controls. Cases were significantly older (28.3 vs. 21.7 years), of higher gravidity (2.7 vs. 1.9), more obese (76.7 vs. 61.7 kg), gained weight more rapidly (0.34 vs. 0.28 kg/week), had more hypertension in this pregnancy (28.2 vs. 2.6%), and there was a higher proportion with a family history of diabetes (41.3 vs. 16.5%) (p less than 0.001 for all comparisons). Because there were significant correlations among the risk factors in both cases and controls, multivariable logistic regression analyses were performed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

The relationship between maternal serum zinc levels during pregnancy and birthweight.

A retrospective follow-up study to ascertain the relationship between the level of serum zinc and its rate of change during gestation and birthweight was conducted in 476 women of lower socioeconomic status. Serum zinc concentrations measured at approximately 16 (early) and 32 weeks (later) in gestation were both found to be significant predictors of birthweight. Even after controlling for gestational age at birth and other determinants of birthweight, for each microgram/dl increase in serum zinc early and later in pregnancy, birthweight increased by 5.8 and 8.6 g, respectively. Furthermore, after adjustment for initial zinc levels both the total change (beta = -7.0, P = 0.0007) and the rate of change (beta = -60.8, P = 0.007) in serum zinc during pregnancy were inversely associated with birthweight, i.e., the larger the fall in serum zinc during pregnancy, the smaller the infant. Low serum zinc level (less than 60 micrograms/dl) late in pregnancy was associated with greater than a five-fold increase in the odds (OR = 5.8, 95% CI = 1.8, 16.4) of giving birth to a low birthweight infant. The results of this study suggest a threshold for maternal serum zinc below which the prevalence of low birthweight increases rapidly.

Adolescent↗
PubMed1991

Autoantibodies in black women with class A1 or class GB diabetes mellitus.

No marker except repeated fasting glucose determinations has proven useful to ascertain prospectively which women with gestational diabetes mellitus will remain euglycemic by diet modification or will require insulin therapy. We screened 183 black women with gestational diabetes mellitus to determine if the presence of islet cell, mitochondrial, nuclear, DNA, parietal cell, smooth muscle, thyroid microsomal, thyroid thyroglobulin autoantibodies, or rheumatoid factor predicted the need for insulin therapy to maintain euglycemia in women with gestational diabetes mellitus. One hundred forty-two women maintained normal fasting plasma glucose levels with dietary modifications and 41 required institution of split-dose insulin therapy. We found no significant differences in the prevalence of these autoantibodies in black women with Class GB versus Class A1 diabetes mellitus. We conclude that screening for autoantibodies in women with gestational diabetes mellitus is not useful in determining which patients will subsequently require insulin therapy during their pregnancies.

Antibodies, Antinuclear↗
PubMed1991

Histocompatibility antigen subtypes in black women with class A1 or class GB diabetes mellitus.

Insulin-dependent diabetes mellitus is associated with an increased frequency of certain histocompatibility antigens located on chromosome six, the most common types being B-8, B-15, DR-3, DR-4, and DR-7. We therefore theorized that screening for these subtypes may allow the identification of those women with gestational diabetes who will remain euglycemic on dietary modification (class A1) compared with those who will require insulin to achieve euglycemia (class GB). From 1982 to 1987, 228 black women with gestational diabetes were screened for the above histocompatibility antigens. As theorized, certain histocompatibility antigen subtypes were more common in women with class GB gestational diabetes mellitus; DR-2 (41.8% versus 23.7% p = 0.015), B-15 (p = 0.07), and DR-3 (p = 0.08). However, because of the low sensitivity (42%), specificity (75%), and positive predictive value (36%), this test is impractical in the clinical management of women with gestational diabetes mellitus.

Black People↗
PubMed1990

A positive association between maternal serum zinc concentration and birth weight.

A study was conducted on a cohort of 476 women (364 black, 112 white), who attended the Jefferson County Health Department clinic for their prenatal care, to ascertain the relationship between maternal serum zinc concentration measured early in pregnancy and birth weight. For all subjects maternal serum zinc was significantly related to birth weight after various independent determinants of birth weight were controlled for. The data in this study indicate a threshold for maternal serum zinc concentration below which the prevalence of low birth weight increases significantly. Pregnant women who had serum zinc concentrations in the lowest quartile had significantly higher prevalence of low birth weight than did those mothers who had serum zinc concentrations in the upper three quartiles during pregnancy. These findings suggest that maternal serum zinc concentration measured early in pregnancy could be used to identify those women at higher risk of giving birth to a low-birth-weight infant.

Adult↗
PubMed1990

Risk factors for gestational diabetes in black population.

In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis.

Adult↗
PubMed1989

The effect of risk assessment in conjunction with health promotion education on compliance with preventive behaviors.

In this study, 55 subjects were given prevention-oriented recommendations from general, detailed nutritional, and Type A personality risk assessments in conjunction with health promotion education. Changes in compliance with health behaviors were measured 13 months after the first assessment, using the same three risk assessment instruments. Based on self-report, a statistically significant number of persons changed from noncompliance to compliance on three nutritional behaviors, three behaviors related to health-promoting exercise and recreation, and one medical screening behavior. A statistically significant reduction in mean from the first to second year was observed for daily sodium intake and percent of calories from fat, and a significant increase in mean percent of time using seatbelts. Though limited by study design, the results provide encouraging evidence in support of the proposition that risk assessment in conjunction with health promotion education can effect positive change in preventive behaviors.

Adult↗