Sarcoidosis and granuloma genes: a family-based study in African-Americans

Rybicki, Benjamin A.; Maliarik, Mary J.; Poisson, Laila; Iannuzzi, Michael C.

doi:10.1183/09031936.04.00005904

Cited by 45 publications

(37 citation statements)

References 45 publications

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“…A major limitation of case-control association studies of candidate genes is that an allelic association may arise if cases and controls were drawn from genetically different populations even though no disease gene association exists. Recently, in a large family-based association study Rybicki et al 43 reported lack of associations with three candidate genes for sarcoidosis that previously had positive associations in studies that used a case control design. [44][45][46] The initial stage of a genome scan is blind to biases toward any specific group of candidate genes; however, to guard against false negatives, liberal P-values are used for follow-up of linkage signals.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

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Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P ¼ 0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

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Section: Discussionmentioning

confidence: 99%

Genome-wide search for sarcoidosis susceptibility genes in African Americans

et al. 2005

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“…One excluded study reported allelic frequencies; the other was family-based study (Rybicki et al 2004;Grutters et al 2002).…”

Section: Data Extractionmentioning

confidence: 99%

“…The remaining five studies not included were family-based studies, studies evaluating serum ACE levels or studies evaluating sarcoidosis symptoms (Csaszar et al 1997;Niimi et al1998;Kawakami et al 1998;Schurmann et al 2001;Rybicki et al 2004).…”

Section: Data Extractionmentioning

confidence: 99%

Role of genetic polymorphisms in ACE and TNF-α gene in sarcoidosis: a meta-analysis

et al. 2007

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A great number of association studies have been performed to identify the genes involved in the etiology and prognosis of sarcoidosis. We performed a systematic review of case-control studies through the PubMed database and evaluated them for a possible inclusion into a meta-analysis in order to assess whether the reported genetic polymorphisms are the risk factors of sarcoidosis. Case-control studies with clear diagnostic criteria and interventions were included. Only investigations of a single polymorphism/gene involvement in sarcoidosis reported more than five times were selected. Aggregating data from 12 studies on ID/ACE polymorphisms, the odds ratio (OR) for sarcoidosis, if the polymorphism was considered under the dominant genetic model, was not significantly increased: 1.19 (95% CI 0.98-1.43); OR under the recessive model was 1.20 (95% CI 0.98-1.46). In seven case-control studies on -308/TNF-a polymorphism, the OR for sarcoidosis if the polymorphism considered under the dominant genetic model was significantly increased at 1.47 (95% CI 1.03-2.08); the OR under the recessive model was 1.39 (95% CI 0.67-2.90). In conclusion, the results showed that the TNF-a genotype could be a significant risk factor for sarcoidosis, whereas the risk of sarcoidosis due to the ACE genotype was not substantially elevated.

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“…Predictably, analysis of T-cell receptor variants has also revealed patterns associated with disease susceptibility or phenotype [46]. However, poor reproducibility has characterized these studies, with substantial interpopulation variability due to population stratification, sampling error, or unsuspected differences in modifier genes/exposures between populations [2,5]. Epidemiologic observations have suggested multiple potential etiologic triggers for sarcoidosis, with the possibility that susceptibility to any putative agent may be a function of the individuals' genetic predisposition.…”

Section: Gene-environment Interactions In Sarcoidosis Evidence For Mamentioning

confidence: 99%

“…In this regard, numerous attempts to define disease susceptibility genes, usually by candidate gene approaches, although more recently using haplotype analysis, have yielded results that are poorly reproducible [5]. More recently, two whole genome scans have yielded differing results, possibly because two different populations were studied [6,7].…”

Section: Introductionmentioning

confidence: 99%

Gene-environment interactions in sarcoidosis: challenge and opportunity

Culver¹,

Newman²,

Kavuru³

2007

Clinics in Dermatology

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Susceptibility to most human diseases is polygenic, with complex interactions between functional polymorphisms of single genes governing disease incidence, phenotype, or both. In this context, the contribution of any discrete gene is generally modest for a single individual, but may confer substantial attributable risk on a population level. Environmental exposure can modify the effects of a polymorphism, either by providing a necessary substrate for development of human disease or because the effects of a given exposure modulate the effects of the gene. In several diseases, genetic polymorphisms have been shown to be context-dependent, i.e. the effects of a genetic variant are realized only in the setting of a relevant exposure. Since sarcoidosis susceptibility is dependent on both genetic and environmental modifiers, the study of gene-environment interactions may yield important pathogenetic information and will likely be crucial for uncovering the range of genetic susceptibility loci. However, the complexity of these relationships implies that investigations of geneenvironment interactions will require the study of large cohorts with carefully-defined exposures and similar clinical phenotypes. A general principle is that the study of gene-environment interactions requires a sample size at least several-fold greater than for either factor alone. To date, the presence of environmental modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA-DQB1, in African-American families. This article reviews general considerations obtaining for the study of gene-environment interactions in sarcoidosis. It also describes the limited current understanding of the role of environmental influences on sarcoidosis susceptibility genes.

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Sarcoidosis and granuloma genes: a family-based study in African-Americans

Cited by 45 publications

References 45 publications

Genome-wide search for sarcoidosis susceptibility genes in African Americans

Genome-wide search for sarcoidosis susceptibility genes in African Americans

Role of genetic polymorphisms in ACE and TNF-α gene in sarcoidosis: a meta-analysis

Gene-environment interactions in sarcoidosis: challenge and opportunity

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