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Rheumatology
Article
Data sources: UnpayWall
Rheumatology
Article . 2012 . Peer-reviewed
Data sources: Crossref
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Genetic polymorphisms inside and outside the MHC improve prediction of AS radiographic severity in addition to clinical variables

Authors: Nerea, Bartolomé; Magdalena, Szczypiorska; Alejandra, Sánchez; Jesús, Sanz; Xavier, Juanola-Roura; Jordi, Gratacós; Pedro, Zarco-Montejo; +5 Authors

Genetic polymorphisms inside and outside the MHC improve prediction of AS radiographic severity in addition to clinical variables

Abstract

The aim of this study was to analyse if single nucleotide polymorphisms (SNPs) inside and outside the MHC region might improve the prediction of radiographic severity in AS.A cross-sectional multi-centre study was performed including 473 Spanish AS patients previously diagnosed with AS following the Modified New York Criteria and with at least 10 years of follow-up from the first symptoms of AS. Clinical variables and 384 SNPs were analysed to predict radiographic severity [BASRI-total (BASRI-t) corrected for the duration of AS since first symptoms] using multivariate forward logistic regression. Predictive power was measured by the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV).The model with the best fit measured radiographic severity as the BASRI-t 60th percentile and combined eight variables: male gender, older age at disease onset and six SNPs at ADRB1 (rs1801253), NELL1 (rs8176785) and MHC (rs1634747, rs9270986, rs7451962 and rs241453) genes. The model predictive power was defined by AUC = 0.76 (95% CI 0.71, 0.80), being significantly better than the model with only clinical variables, AUC = 0.68 (95% CI 0.63, 0.73), P = 0.0004. Internal split-sample analysis proved the validation of the model. Patient genotype for SNPs outside the MHC region, inside the MHC region and clinical variables account for 26, 38 and 36%, respectively, of the explained variability on radiographic severity prediction.Prediction of radiographic severity in AS based on clinical variables can be significantly improved by including SNPs both inside and outside the MHC region.

Keywords

Adult, Male, Calcium-Binding Proteins, Nerve Tissue Proteins, Middle Aged, Polymorphism, Single Nucleotide, Sensitivity and Specificity, Severity of Illness Index, Cohort Studies, Major Histocompatibility Complex, Radiography, Cross-Sectional Studies, Logistic Models, ROC Curve, Predictive Value of Tests, Humans, Female, Genetic Predisposition to Disease, Receptors, Adrenergic, beta-1, Follow-Up Studies

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Average
Average
Top 10%
bronze