Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested by several authors. Autoantibodies against HSPs have been associated with such autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD mouse model of diabetes. Moreover, genes for the major 70,000-M(r) HSP (HSP70) are located within the MHC. To investigate a potential association of an HSP70-2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM. With the enzyme PstI, as reported previously, two HSP70-2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele was found more frequently on diabetic haplotypes compared with control haplotypes (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the conservation of alleles on extended haplotypes we previously reported to be associated with diabetes on initial analysis of families. Twenty-three of 26 diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of 9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele (P = 8 x 10(-7) DR3 vs. DR2 haplotypes). The alleles were equally distributed among DR4 haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No independent association between HSP70 gene polymorphism and IDDM. 135 54

We investigate whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish population. A HSP70-2 PstI polymorphism was characterized by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified genomic DNA in 90 SLE patients and 117 controls. The PstI site containing allele (B) was significantly increased in SLE patients compared to healthy controls. This was due to a significant increase in the BB homozygous genotype in patients, particularly in those with diffuse proliferative nephritis. Neither allelic nor genotypic differences were detected when compared by the presence or absence of DR3. The HSP70-2 B allele seems tightly linked to the human leucocyte antigen (HLA) haplotypes carrying susceptibility to SLE in our population. An independent role for this gene cannot be confirmed due to its linkage with HLA DR3.
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PMID:Polymorphism of the heat-shock protein gene HSP70-2 in systemic lupus erythematosus. 755 54

Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P < 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC < 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3-HSP70-2A (D = 0.03, D' = 0.67, P < 0.01); HLA-DR1-HSP70-2A (D = 0.03, D' = 0.86, P < 0.01) and HLA-DR8-HSP70-2B (D = 0.02, D' = 0.46, P = 0.02). Our data indicate that HSP70-2 gene polymorphism as opposed to the other ethnic groups does not appear to be relevant in SLE susceptibility in Mexican patients and that the distribution of the different alleles depend on the frequency of HLA alleles associated with them.
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PMID:Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population. 1119 83

The human major histocompatibility complex (MHC) class III region spanning approximately 760 kb is characterized by a remarkably high gene density with 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loci to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loci. However, it has been difficult to precisely localize these susceptibility loci to a single gene due to a paucity to date of polymorphic markers in the HLA class III region. To facilitate disease mapping within this region, we have analyzed 2 approximately 5 bases short tandem repeats (microsatellites) in this region. A total of 297 microsatellites were identified from the genomic sequence, consisting of 69 di-, 62 tri-, 107 tetra-, and 59 penta-nucleotide repeats. It was noted that among them as many as 17 microsatellites were located within the coding sequence of expressed genes (NOTCH4, PBX2, RAGE, G16, LPAAT, PPT2, TNXB, P450-CYP21B, G9a, HSP70-2, HSP70-1, HSP-hom, MuTSH5 and BAT2). Eight microsatellite repeats were collected as polymorphic markers due to their high number of alleles (11.9 on average) as well as their high polymorphic content value (PIC) (0.63). By combining the 38 and the 22 polymorphic microsatellites we have previously collected in the HLA class I and class II regions, respectively, we have now established a total of 68 novel genetic markers which are uniformly interspersed with a high density of one every 63.3 kb throughout the HLA region. This collection of polymorphic microsatellites will enable us to search for the location of any disease susceptible loci within the HLA region by association analysis.
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PMID:New polymorphic microsatellite markers in the human MHC class III region. 1155 64

HLA alelles with susceptibility to systemic lupus erythematosus (SLE) have been found in many ethnic groups. In addition, some neighboring genes such as TNF-alpha and HSP70, that may contribute to this disease have also been described. Interestingly some of the genetic associations differ among several ethnic groups, which might suggest that ethnicity plays an important role in the predisposition to SLE. In this study, we analyze gene frequencies of HLA-DRB1, DQA1, DQB1, HSP70-2 alelles and the polymorphism of TNF-alpha promoter region among 81 Mexican mestizo SLE patients. A control group of 99 healthy Mexican mestizos was included. We found that the HLA-DRB1*0301-DQA1*0501-DQB1*0201 haplotype was significantly increased in SLE patients compared to healthy controls (p=0.01, OR=2.97, IC 95%=1.18-7.68). The DRB1*1501 allele was more frequent among patients than among controls. A significantly decreased frequency of the HLA-DRB1*0802 alelle in SLE patients was also observed. Since the HLA alelles associated with SLE are uncommon in Mexican ethnic groups, we performed admixture estimates analysis and found that the incorporation of SLE susceptibility markers in Mexican mestizo groups might have come from genetic admixture with Caucasian populations.
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PMID:[Influence of alleles and haplotypes of the main histocompatibility complex on the susceptibility to systemic lupus erythematosus in the Mexican population]. 1687 46