Synergistic effect betweenIL-10 andbcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

Mehrian, Ruty; Quismorio, Francisco P.; Strassmann, Gideon; Stimmler, Mary M.; Horwitz, David A.; Kitridou, Rodanthi C.; Gauderman, W. James; Morrison, John L.; Brautbar, Chaim; Jacob, Chaim O.

doi:10.1002/1529-0131(199804)41:4<596::aid-art6>3.0.co;2-2

Cited by 146 publications

(98 citation statements)

References 26 publications

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“…13 Different polymorphisms were identified both in the 5' flanking region [14][15][16][17][18][19][20] and, more recently, in the transcribed region 21 of the IL10 gene including two microsatellites at position À4000 (IL10 15 ) and À1100 (IL10 16 ). One of the two microsatellites, IL10.G, has been shown to be associated to SLE by three independent studies, including ours [22][23][24] although this was not supported by a fourth work. 25 In our study the IL10.G-140bp allele was significantly increased in Italian SLE patients.…”

Section: Introductionmentioning

confidence: 57%

“…[22][23][24] The association with the IL10 microsatellite could be due to linkage disequilibrium with some causal variation in another closely linked gene. Three genes belonging to the IL10 family (IL19, IL20 and IL24) have been recently mapped immediately telomeric to IL10 at a distance of 60 , 82 and 112 kb respectively from IL10G, and are possible candidates.…”

Section: Discussionmentioning

confidence: 99%

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Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

et al. 2002

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Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position À1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5 0 flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibiliy.

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Section: Introductionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

et al. 2002

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“…Alleles of all three genes were found to be associated with SLE in a study of Mexican-Americans [61]. In the same study, a synergistic effect between alleles of the IL-10 and bcl-2 genes in determining susceptibility SLE was found [61].…”

Section: Studies Of Candidate Genesmentioning

confidence: 91%

The Genetics of Systemic Lupus Erythematosus

Lindqvist

Alarcón‐Riquelme

1999

Scand J Immunol

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Lindqvist AKB, Alarcón-Riquelme ME. The Genetics of Systemic Lupus Erythematosus. Scand J Immunol 1999;50:562-571. There is considerable evidence that the development of systemic lupus erythematosus (SLE) has a strong genetic basis. For more than 20 years, much effort has been made to understand the genetics of SLE. Association studies in humans suggest the existence of genetic effects by the alleles encoded in the HLA, deficiencies in the complement genes and the low-affinity variants of Fc␥-receptors. In mouse models of SLE at least 13 loci have been identified, including the MHC, linked to lupus-related phenotypes such as nephritis and production of autoantibodies. Recently, linkage studies have been performed in human SLE; one investigating a candidate region based on synteny to a murine susceptibility locus and four genome-wide linkage studies in various populations. Linkage was demonstrated to several chromosomal regions, some of which are syntenic to murine lupus susceptibility loci. Interestingly, many of the identified chromosomal regions co-localise with loci implicated in other autoimmune diseases.

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“…Some evidence has been obtained for possible association with SLE and alleles at Bcl-2, CTLA4, the T cell receptors, prolactin, tumor necrosis factor (TNF) and TNF receptors. [92][93][94][95][96][97][98] Even in aggregate, however, these effects are too small to explain the genetics of SLE. Therefore, other genes still remain to be identified.…”

Section: Fc␥ Receptorsmentioning

confidence: 99%

“…106 To date, no study has observed an association between the IL10.R microsatellite and SLE. Mehrian et al 92 …”

Section: Interleukin-10mentioning

confidence: 99%

The genetics of systemic lupus erythematosus: putting the pieces together

2002

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Synergistic effect betweenIL-10 andbcl-2 genotypes in determining susceptibility to systemic lupus erythematosus

Abstract: The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.

Cited by 146 publications

References 26 publications

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

The Genetics of Systemic Lupus Erythematosus

The genetics of systemic lupus erythematosus: putting the pieces together

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