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Major genes regulating total serum immunoglobulin E levels in families with asthma.

ABSTRACT: Immunoglobulin E (IgE) has a major role in the pathogenesis of allergic disorders and asthma. Previous data from 92 families, each identified through a proband with asthma, showed evidence for two major genes regulating total serum IgE levels. One of these genes mapped to 5q31-33. In the current study, the segregation analysis was extended by the addition of 108 probands and their families, ascertained in the same manner. A mixed recessive model (i.e., major recessive gene and residual genetic effect) was the best-fitting and most-parsimonious one-locus model of the segregation analysis. A mixed two-major-gene model (i.e., two major genes and residual genetic effect) fit the data significantly better than did the mixed recessive one-major-gene model. The second gene modified the effect of the first recessive gene. Individuals with the genotype aaBB (homozygous high-risk allele at the first gene and homozygous low-risk allele at the second locus) had normal IgE levels (mean 23 IU/ml), and only individuals with genotypes aaBb and aabb had high IgE levels (mean 282 IU/ml). A genomewide screening was performed using variance-component analysis. Significant evidence for linkage was found for a novel locus at 7q, with a multipoint LOD score of 3. 36 (P=.00004). A LOD score of 3.65 (P=.00002) was obtained after genotyping additional markers in this region. Evidence for linkage was also found for two previously reported regions, 5q and 12q, with LOD scores of 2.73 (P=.0002) and 2.46 (P=.0004), respectively. These results suggest that several major genes, plus residual genetic effects, regulate total serum IgE levels.

SUBMITTER: Xu J

PROVIDER: S-EPMC1288559 | biostudies-other | 2000 Nov

REPOSITORIES: biostudies-other

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Major genes regulating total serum immunoglobulin E levels in families with asthma.

Xu J J Postma D S DS Howard T D TD Koppelman G H GH Zheng S L SL Stine O C OC Bleecker E R ER Meyers D A DA

American journal of human genetics 20001006 5

Immunoglobulin E (IgE) has a major role in the pathogenesis of allergic disorders and asthma. Previous data from 92 families, each identified through a proband with asthma, showed evidence for two major genes regulating total serum IgE levels. One of these genes mapped to 5q31-33. In the current study, the segregation analysis was extended by the addition of 108 probands and their families, ascertained in the same manner. A mixed recessive model (i.e., major recessive gene and residual genetic e ...[more]

PMID: 11023809

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Project description:BackgroundOccupational exposures to chromium (Cr), which can have adverse effects on immune function, have not yet been extensively investigated. Hexavalent chromium (Cr (VI)), used in mineral tanning processes, poses a threat to the health of workers in the leather tanning industry.ObjectivesThe aim of the present study was to evaluate the effects of long-term Cr exposure on the physical health and immunological parameters of male tannery workers in Bangladesh compared with a control group.MethodsA health examination was performed with tannery workers (N=195) and control subjects (N=125) by physicians, demographic data were recorded in questionnaires and peripheral blood samples were collected. Serum Cr levels were analyzed by an atomic absorption spectrophotometer (AAS), immunoglobulin (Ig)G, IgA, and complement components C3 and C4 were determined by nephelometry, IgE was measured by sandwich enzyme-linked immunosorbent assay and complement function was assayed by bactericidal activity.ResultsThe mean duration of work exposure for the tanners was 9.4±7.1 years. Their body mass index (21.8±3.0 kg/m2), was not significantly different from the controls (22.7±3.2 kg/m2). The mean serum level of Cr in 30 long-term exposed tannery workers (26.97±21.11 μg/dL) was significantly higher than that of 30 randomly selected control subjects (7.38±6.81 μg/dL). The tannery workers had rough skin, rashes, itchy and decolorized skin, allergic diseases and respiratory illness, and had significantly lower levels of serum IgG, IgA, C3 and C4, but significantly higher levels of IgE than the controls. IgG, IgA and C3 levels were all inversely associated with Cr, while IgG, IgE and bactericidal activity showed an inverse correlation with duration of exposure.ConclusionsThe results of the present study suggest that chronic exposure to Cr is associated with impaired immune function in male tannery workers.Participant consentObtained.Ethics approvalThe present study was approved by the Ethical Review Committee of the faculty of Biological Sciences, University of Dhaka, Bangladesh.Competing interestsThe authors declare no competing financial interests.

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Major genes regulating total serum immunoglobulin E levels in families with asthma.

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Major genes regulating total serum immunoglobulin E levels in families with asthma.

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