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D L Duffy

Publications and source records attributed to D L Duffy.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: We have recently conducted a genome-wide screening for genes influencing Dermatophagoides pteronyssinus-specific IgE responsiveness as a part of the Collaborative Study on the Genetics of Asthma (CSGA), which showed evidence for linkage in some regions, including chromosomes 5131-q33 and 11q13 in African American families. OBJECTIVES: To clarify relative contributions of these regions to atopy in the same African American population, we have conducted further genetic linkage studies of specific IgE responses toward common inhaled allergens. METHODS: We studied 328 individuals in 58 African American families participating in the CSGA. Specific IgE responses toward Dermatophagoides farinae, cat, dog, American cockroach, rye grass, and Bermuda grass, as measured by skin tests, were used for multipoint linkage analysis with polymorphic markers on chromosomes 5q31-q33 and 11q13. RESULTS: Specific IgE response toward American cockroach showed evidence for linkage to chromosomes 5q31-q33 (P = .0050) and 11q13 (P = .017). Specific IgE response toward dog showed evidence for linkage with chromosome 5q31-q33 (P = .0043). Evidence for linkage with chromosome 11q13 was obtained for specific IgE responses toward Dermatophagoides farinae (P = .012), cat (P = .035), and Bermuda grass (P = .017). The presence of a positive ST response for at least 1 of 30 common allergens showed evidence for linkage to chromosomes 5q31-q33 (P = .017) and 11q13 (P = .00058). CONCLUSIONS: These data support that genes on both chromosomes 5q31-q33 and 11q13 confer susceptibility to upregulated IgE-mediated immune responses in this African American population. The putative genes on chromosomes 5q31-q33 and 11q13, however, showed contrasting effects on atopy, which may result from strong gene-environmental interactions.

Administration, Inhalation↗
PubMed1998

Immunoblotting analysis of twin sera provides evidence for limited genetic control of specific IgE to house dust mite allergens.

BACKGROUND: Although some studies have shown genetic control of specific IgE responses to purified grass allergens, studies with other allergens have not supported this. The extent of such control for house dust mite (HDM) (Dermatophagoides pteronyssinus) allergens is unclear. OBJECTIVE: We sought to determine the extent to which genetic factors control the specificity of IgE responses to individual HDM allergens by comparing the immunoblot patterns of IgE binding of serum from monozygotic and dizygotic members of a large cohort of Australian twins. METHODS: HDM proteins separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis were immunoblotted with sera from 317 twin pairs in which at least one twin had at least a weak HDM skin test response. Concordance levels for IgE binding to the individual HDM components were compared in the subset of 142 pairs of twins in which both twins were allergic to HDMs (skin prick test wheal diameter, > 3 mm). RESULTS: Over all 36 blotted bands, the mean case-wise concordance was 41% for monozygotic twins and 17% for dizygotic twins. Of the components detected, only those of molecular weights 23 kd and 16 kd were significantly different between the groups (p < 0.01). Differences observed between the monozygotic and dizygotic twins could be partly explained by overall IgE hyperresponsiveness. CONCLUSION: Evidence for genetic control of IgE responses to 36 IgE-binding HDM components from a large sample of twins showed significant differences in concordance for two components and nonsignificant differences for several others. In the monozygotic twins, concordance never exceeded 67% for any band, and most monozygotic individuals recognized components their co-twin did not. Genetic control of overall atopy in monozygotic twins is far stronger than that controlling specific sensitization to HDM allergens.

Allergens↗
PubMed1998

Limited genetic control of specific IgE responses to rye grass pollen allergens in Australian twins.

BACKGROUND: Both genetic and environmental factors are thought to contribute to specific IgE responses, however, the relative contribution of each in the responses to individual ryegrass pollen allergens is largely unknown even though some responses to allergens have been linked to certain HLA complexes. OBJECTIVE: Using a large group of monozygotic and dizygotic twins, this study was designed to investigate the IgE binding profiles of individual ryegrass pollen (Lolium perenne) components to assess the relative contribution of genetic and environmental factors in determining IgE responses to specific allergens. METHODS: Ryegrass pollen proteins were separated by electrophoresis and immunoblotted with sera from 191 pairs of twins where at least one sibling had a SPT > 2 mm to perennial ryegrass. Concordance levels for individual ryegrass pollen components were compared between monozygotic and dizygotic twins in a subset group where both twins had SPT > 3 mm to perennial ryegrass. RESULTS: Immunoblotting revealed 23 individual IgE-binding components from ryegrass pollen. Although there was a significantly greater proportion of monozygotic twins with SPT wheals greater than 3 mm when compared with the dizygotic twins, the mean case-wise concordance for the immunoblot components was similar for both groups of twins. The mean case-wise concordance when at least four pairs of sera were involved was 44% for the MZ twins (n=11 components) and 45% for the DZ twins (n=12 components). We found no significant differences in concordance levels for any of the 23 individual components including allergens previously associated with HLA. CONCLUSION: Evidence for genetic control of allergen-specific IgE responses in a large population sample of twins to individual ryegrass allergens is limited, indicating that the IgE responses to specific ryegrass pollen allergens are determined largely by environmental factors.

Adolescent↗
PubMed1998

Genetic and environmental risk factors for asthma: a cotwin-control study.

In complex diseases of genetic etiology such as asthma and atopy, it is difficult to differentiate causes of disease from consequences, and quantitate the importance of such causative factors. We examined possible risk factors for the development of wheezing and bronchial hyperresponsiveness in a cotwin-control study nested within a larger community-based twin-family study. In 62 monozygotic (MZ) twin pairs discordant for a history of wheezing, skin prick test to house dust extract was the most important discriminator, followed by sensitization to cat and cockroach allergens. In contrast, 62 dizygotic (DZ) discordant twin pairs differed additionally in sensitization to grass pollens and fungi. Markers such as serum haptoglobin, serum magnesium, and alpha-1-antitrypsin levels did not differ significantly between discordant twins. This MZ/DZ difference suggests that pollen allergy in asthmatics is more an epiphenomenon due to a genetic correlation between asthma and the allergic diathesis, whereas indoor allergens are likely to be direct environmental causes of asthma.

Adult↗
PubMed1998

A factor analysis of associations among self-reported immune related symptoms in a large twin sample.

We examined the cumulative prevalences of 22 symptoms thought to reflect immune system function reported in a questionnaire mailed to 7616 Australian twins. The associations between symptoms and demographic variables were expressed in terms of polychoric or polyserial correlations, and a principal components analysis performed. Factors representing underlying propensities respectively to allergic disease, various minor infections, diseases associated with aging such as arthritis, skin disease, and respiratory tract infection were extracted. Possible processes underlying these symptom clusters and the relative strengths and weaknesses of this type of analysis are discussed.

Adult↗
PubMed1997

Application of transmission disequilibrium tests to nonsyndromic oral clefts: including candidate genes and environmental exposures in the models.

Extensive epidemiological and genetic studies of the cause of oral clefts have demonstrated strong familial aggregation but have failed to yield definitive evidence of any single genetic mechanism. We used the transmission/disequilibrium test (TDT) to investigate the relationship between oral clefts and markers associated with five candidate genes by utilizing 160 parent-offspring trios. Conditional logistic regression models extended the TDT to include covariates as effect modifiers, thus permitting tests for gene-environment interactions. For four of these candidates [transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), retinoic acid receptor (RARA), and the proto-oncogene BCL3], we detected modestly elevated odds ratios for the transmission of one marker allele to cleft probands when all the trios were analyzed together. These odds ratios increased when information on type of cleft, race, family history, or maternal smoking were incorporated as effect modifiers. We detected significant interaction between maternal smoking and the transmission of alleles for markers near TGFA and TGFB3; excess transmission of allele 3 at BCL3 was most significant among cleft lip probands; and the odds ratios for transmission of alleles at D19S178 and THRA1 were significant when ethnic group was included in the model. We suggest that utilizing an analytical strategy that allows for stratification of data and incorporating environmental effects into a single analysis may be more effective for detecting genes of small effect.

B-Cell Lymphoma 3 Protein↗
PubMed1997

Evidence for linkage of chromosome 12q15-q24.1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study.

Linkage of asthma and high total serum IgE levels to chromosome 12q15-q24.1 has been recently described. To evaluate this region further in regard to total IgE responsiveness, we genotyped 52 unrelated German children with persistently "high" total serum IgE (selected from a noninterventional prospective multicenter cohort study) and their parents. We carefully defined a most extreme IgE phenotype and analyzed it as a dichotomous trait. We tested for linkage between high total IgE concentrations and nine polymorphic microsatellite markers on chromosome 12q15-q24.1 using the transmission/disequilibrium test. Evidence for linkage and allelic association for high total IgE was observed for four markers in this region. This study demonstrates the value of using extreme phenotypes in genetic analysis of a complex quantitative trait.

Child, Preschool↗
PubMed1997

A comprehensive analysis of complex traits in problem 2A.

We used descriptive analysis to investigate the relationship between affection status and five quantitative traits (Q1-Q5) in Problem 2A and results suggested the five quantitative traits fall into two groups. The first group comprised three strongly correlated traits, Q1-Q3, which underlie affection status, and the second group comprised Q4 and Q5, which are not directly related to affection status. Segregation and linkage analyses of traits Q1-Q3 and affection status from the first replicate detected one of the major loci for Q1 (MG1) linked to marker 14 on chromosome 5 (D5G14). Because our segregation analysis failed to show evidence of a major locus effect on Q2, and we overlooked the interaction between MG3 and sex, we did not detect either MG2 or MG3. Using Haseman-Elston sib-pair analysis [Haseman and Elston, 1972], we also examined the statistical power of Q1 and type I error rate (using the environmental factor as an index), for the remaining 199 replicates in the context of a genome screen.

Chromosome Mapping↗
PubMed1997

Maternal cigarette smoking and oral clefts: a meta-analysis.

OBJECTIVE: A meta-analysis was performed to estimate the association between maternal cigarette smoking and the risk of having a child with a nonsyndromic oral cleft (NSOC). DESIGN: Studies published from 1966 through 1996 were retrieved using MEDLINE, Current Contents, bibliographies, and other sources. MEDLINE and Current Contents search terms included "oral clefts," "cigarette smoking," "birth defects," and "congenital malformations." Cohort and case-control studies that enrolled oral cleft patients [cleft lip with or without cleft palate (CL/P), cleft palate (CP), or both] and controls, and presented information on maternal cigarette exposure during pregnancy were included in the analysis. Descriptive and outcome data from each study were independently abstracted by two authors. RESULTS: The overall odds ratio of the 11 studies satisfying criteria was 1.29 [95% confidence interval (CI), 1.18 to 1.42] for CL/P and 1.32 (95% CI: 1.10 to 1.62) for CP, indicating a small increase risk of having a child with either a CL/P or a CP for mothers who smoke during the first trimester of the pregnancy. CONCLUSIONS: These analyses suggest a small but statistically significant association between maternal cigarette smoking during the first trimester of gestation and increased risk of having a child with a CL/P or CP.

Cleft Lip↗
PubMed1997

Genetic effects on variation in red-blood-cell folate in adults: implications for the familial aggregation of neural tube defects.

Recent studies have implicated folic acid as an important determinant of normal human growth, development, and function. Insufficient folate levels appear to be a risk factor for neural tube defects (NTD), as well as for several chronic diseases of adulthood. However, relatively little is known about the factors that influence folate status in the general population. To estimate the relative contribution of genetic and nongenetic factors to variation in folate, we have evaluated red blood cell (RBC) folate levels in 440 pairs of MZ twins and in 331 pairs of DZ twins. The data were best described by a model in which 46% of the variance in RBC folate was attributable to additive genetic effects, 16% of the variance was due to measured phenotypic covariates, and 38% of the variance was due to random environmental effects. Moreover, the correlations for RBC folate in MZ co-twins (r = .46) and in repeat measures from the same individual (r = .51) were very similar, indicating that virtually all repeatable variation in RBC folate is attributable to genetic factors. On the basis of these results, it would seem reasonable to initiate a search for the specific genes that influence RBC folate levels in the general population. Such genes ultimately may be used to identify individuals at increased risk for NTD and other folate-related diseases.

Adult↗
PubMed1996

Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations.

To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum IgE concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to this region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) controlling asthma and the associated "high total IgE" trait.

Adolescent↗
PubMed1995

Osteoporosis in rheumatoid arthritis. A monozygotic co-twin control study.

OBJECTIVE: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study. RESULTS: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites. CONCLUSION: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.

Arthritis, Rheumatoid↗
PubMed1995

Screening a 2 cM genetic map for allelic association: a simulated oligogenic trait.

In this paper, we explore the use of a variety of familial transmission tests (and case-control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5-10 years. We demonstrate a form of the transmission-disequilibrium test extended to multiallele systems. The methods used were log-linear and related models implemented largely using standard statistical packages.

Alleles↗
PubMed1994

Heterogeneity of melanoma risk in families of melanoma patients.

While it is recognized that relatives of melanoma patients are at increased risk for this disease, the source and extent of variation in melanoma risk between families of melanoma cases is unknown. Heterogeneity of familial melanoma risk was assessed among the families (comprising 7,666 first-degree relatives) of 1,149 cutaneous melanoma cases diagnosed in Queensland, Australia, between 1982 and 1987. The measure of familial melanoma risk was based on the number of cases of melanoma in the family in excess of those predicted from the age-, sex-, and birth cohort-specific cumulative incidences of melanoma among all relatives in the sample. Probands over-reported melanoma occurrence among their relatives, with a false positive reporting rate of 44.5% (216 false reports out of 485). Only medically verified cases among relatives were included in the analysis. There was statistically significant heterogeneity in family risk, with 53 (4.7%) of the total 1,116 unrelated families containing significantly more melanoma cases than expected considering the size of the family, and the age, sex, and birth cohort distributions of family members. In univariate analyses, members of the high-risk families were significantly more likely to have poor ability to tan, a propensity to sunburn, fair skin color, red hair, and many melanocytic nevi. When all variables were included simultaneously in a multiple logistic regression model, only the associations with tanning ability, skin color, and number of nevi remained significant. There were no significant differences overall between high-risk and other families in the sites and ages at diagnosis of melanoma, although melanomas on variably sun-exposed sites (trunk and legs) were diagnosed earlier in the high-risk families, independent of the stage at diagnosis.

Adult↗