The Data and Statistical Analysis

Tiwari, Jawahar L.; Terasaki, Paul I.

doi:10.1007/978-1-4613-8545-5_3

Cited by 78 publications

(53 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, since the contribution of immunogenetic markers is more relevant for the clinical course and outcome, HLA genotyping should be considered once the diagnosis of RA has been established. This is in contrast to HLA-B27-associated diseases, particularly ankylosing spondylitis, in which the determination of HLA-B27 contributes to the diagnosis (60). Furthermore, the impact of strong HLA predictors, such as DR4 and HVR3 shared epitope, is already apparent at an early stage of the disease and within a relatively short followup period.…”

Section: Discussionmentioning

confidence: 89%

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis

Wagner

Kaltenhäuser

Sauer

et al. 1997

Arthritis & Rheumatism

140

View full text Add to dashboard Cite

Objective. To evaluate HLA markers as early prognostic factors for disease severity in rheumatoid arthritis (RA).Methods. HLA genotyping was carried out in a retrospective analysis of 66 RA patients and in a prospective study of 55 RA patients and 87 healthy controls using polymerase chain reaction-based methods for HLA-DRB1 specificities, DR4 alleles, and their linked DQBl alleles, as well as HLA-B27. The clinical course of RA was assessed by clinical and radiologic scores. The impact of HLA markers was evaluated by epidemiologic means in addition to modeling using multiple logistic regression analysis.Results. Shared epitope-positive (HVR3+) DR4 alleles and the HVR3 amino acid cassette QKRAA were associated with RA in both longstanding (relative risk [RR] 3.34 and 3.19) and recent-onset (RR 2.1 and 2.37) RA. In longstanding RA, radiologic evidence of severe joint destruction (Larsen score >1.62) was seen more often in HVR3 shared epitopc+positive patients than in epitope-negative patients (odds ratio [OR] = 25.67, 2 = 13.59, P = 0.0003). Moreover, rank sum analysis of Larsen indices indicated significantly higher ranking for the presence of the RA-associated HVR3 cassettes (QKRAA, QRRAA) when expressed on a DR4 allele (P < 0.0001). In the prospective study, DR4-positive pa- tients had a significantly increased risk (OR = 13.75, P = 0.00083) of developing bony erosions. In addition, HVR3 epitope-positive DR4-positive individuals had significantly higher Larsen indices than did epitopenegative patients (P = 0.0083). In particular, the presence of the HVR3 epitope on DR4 resulted in an increased a posteriori likelihood (0.91) of developing early erosive disease compared with an a priori risk of 0.62. Conversely, the likelihood decreased to a minimum of 0.35 when the HVR3 epitope was absent.

show abstract

Section: Discussionmentioning

confidence: 89%

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis

Wagner

Kaltenhäuser

Sauer

et al. 1997

Arthritis & Rheumatism

140

View full text Add to dashboard Cite

show abstract

“…28 Odds ratios were calculated using Woolf's formula 29 and chi-square or Fisher's exact test when appropriate was used to test for statistical significance. Unless otherwise stated the P-values presented are not corrected for number of comparisons.…”

Section: Discussionmentioning

confidence: 99%

Evidence of at least two type 1 diabetes susceptibility genes in the HLA complex distinct from HLA-DQB1, -DQA1 and –DRB1

et al. 2003

View full text Add to dashboard Cite

Susceptibility to, and protection against development of type 1 diabetes (T1D) are primarily associated with the highly polymorphic exon 2 sequences of the HLA class II genes: DQB1, DQA1 and DRB1. However, several studies have also suggested that additional genes in the HLA complex influence T1D risk, albeit to a lesser degree than the class II genes. We have previously shown that allele 3 of microsatellite marker D6S2223, 4.9 Mb telomeric of DQ in the extended class I region, is associated with a reduction in risk conferred by the DQ2-DR3 haplotype. Here we replicate this finding in two populations from Sweden and France. We also show that markers in the HLA class II, III and centromeric class I regions contribute to the DQ2-DR3 associated risk of T1D, independently of linkage disequilibrium (LD) with both the DQ/DR genes and the D6S2223 associated gene. The associated marker alleles are carried on the DQ2-DR3-B18 haplotype in a region of strong LD. By haplotype mapping, we have located the most likely location for this second DQ2-DR3 haplotype-modifying locus to the 2.35 Mb region between HLA-DOB and marker D6S2702, located 970 kb telomeric of HLA-B.

show abstract

“…The P values were corrected for the number of comparisons made (Pc) using the Bonferroni inequality method (20). Pc values Ͻ0.05 were considered significant.…”

Section: Discussionmentioning

confidence: 99%

Association of the p22phox Component of NAD(P)H Oxidase With Susceptibility to Diabetic Nephropathy in Patients With Type 1 Diabetes

2003

View full text Add to dashboard Cite

OBJECTIVE -Increased production of reactive oxygen species (ROS) in diabetes is thought to play a major role in the pathogenesis of diabetic microvascular complications such as nephropathy and retinopathy. The NAD(P)H oxidase complex is an important source of ROS in the vasculature. The p22 subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site, together with a A640G in the 3Ј untranslated region. The aim was to investigate the frequency of these polymorphisms in 268 patients with type 1 diabetes with or without microvascular complications.RESEARCH DESIGN AND METHODS -There was a highly significant increase in the frequency of the T/T242 genotype in patients with nephropathy compared with those with retinopathy alone or no microvascular disease after 20 years' diabetes duration (uncomplicated) or normal healthy control subjects (33.3 vs. 6.5, 5.7, and 0.0%, respectively, P Ͻ 0.000001). Furthermore, the T242/G640 haplotype was found in 39.4% of the patients with nephropathy but in only 26.5% of the patients with retinopathy and 15.3 and 10.6% of the uncomplicated and normal control subjects, respectively. RESULTS -When these variants of NAD(P)H oxidase were analyzed together with aldose reductase (5ЈALR2) susceptibility genotypes, Ͼ46.0% of the patients with nephropathy possessed a T242 allele with the Z-2 5ЈALR2 allele compared with only 11.2% of the uncomplicated patients (P Ͻ 0.00003).CONCLUSIONS -In conclusion, these results suggest NAD(P)H oxidase together with the polyol pathway may contribute to the pathogenesis of diabetic nephropathy. Diabetes Care 26:3111-3115, 2003P revious studies have demonstrated an important role for genetic factors in the development of the long-term microvascular complications of diabetes (1-3). Recent attention has focused on polymorphisms of genes that are implicated in glucose metabolism as well as anti-and pro-oxidative stress, which may be implicated in the genetic susceptibility to diabetic microvascular complications (4 -6). It is thought that excess flux through the polyol pathway provides a major source of reactive oxygen species (ROS) and oxidative stress due to the depletion of the cofactors NADPH and NAD ϩ and their regeneration by NAD(P)H oxidase (7-9). During this process, NAD(P)H oxidase generates ROS, including superoxide and hydrogen peroxide, highlighting the important role of NAD(P)H oxidase as a source of ROS in the vascular system. NAD(P)H oxidase is composed of a number of subunits and appears to be widely distributed, being present in neutrophils, fibroblasts, vascular smooth muscle cells, and endothelial and mesangial cells (10 -13). The gene coding for the p22 subunit of NAD(P)H oxidase is polymorphic, including a C242T transition that results in the replacement of histidine by tyrosine at amino acid 72 of the putative heme binding site. These genetic variants have been associated with coronary heart disease, although the results have been inconsistent (14 -17). The C242T polymorphism appear...

show abstract

The Data and Statistical Analysis

Cited by 78 publications

References 26 publications

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis

HLA markers and prediction of clinical course and outcome in rheumatoid arthritis

Evidence of at least two type 1 diabetes susceptibility genes in the HLA complex distinct from HLA-DQB1, -DQA1 and –DRB1

Association of the p22phox Component of NAD(P)H Oxidase With Susceptibility to Diabetic Nephropathy in Patients With Type 1 Diabetes

Contact Info

Product

Resources

About