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Developing a Risk-scoring Model for Ankylosing Spondylitis Based on a Combination of HLA-B27, Single-nucleotide Polymorphism, a

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pmrc
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2018-05-17 14:38
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Jung, S. H., Cho, S. M., Yim, S. H., Kim, S. H., Park, H. C., Cho, M. L., ... & Chung, Y. J. (2016). Developing a Risk-scoring Model for Ankylosing Spondylitis Based on a Combination of HLA-B27, Single-nucleotide Polymorphism, and Copy Number Variant Markers. The Journal of Rheumatology, 43(12), 2136-2141.

DOI:10.3899/jrheum.160347
IF(2015):3.236

Abstract

Objective: To develop a genotype-based ankylosing spondylitis (AS) risk prediction model that is more sensitive and specific than HLA-B27 typing.

Methods: To develop the AS genetic risk scoring (AS-GRS) model, 648 individuals (285 cases and 363 controls) were examined for 5 copy number variants (CNV), 7 single-nucleotide polymorphisms (SNP), and an HLA-B27 marker by TaqMan assays. The AS-GRS model was developed using logistic regression and validated with a larger independent set (576 cases and 680 controls).

Results: Through logistic regression, we built the AS-GRS model consisting of 5 genetic components: HLA-B27, 3 CNV (1q32.2, 13q13.1, and 16p13.3), and 1 SNP (rs10865331). All significant associations of genetic factors in the model were replicated in the independent validation set. The discriminative ability of the AS-GRS model measured by the area under the curve was excellent: 0.976 (95% CI 0.96–0.99) in the model construction set and 0.951 (95% CI 0.94–0.96) in the validation set. The AS-GRS model showed higher specificity and accuracy than the HLA-B27–only model when the sensitivity was set to over 94%. When we categorized the individuals into quartiles based on the AS-GRS scores, OR of the 4 groups (low, intermediate-1, intermediate-2, and high risk) showed an increasing trend with the AS-GRS scores (r2 = 0.950) and the highest risk group showed a 494× higher risk of AS than the lowest risk group (95% CI 237.3–1029.1).

Conclusion: Our AS-GRS could be used to identify individuals at high risk for AS before major symptoms appear, which may improve the prognosis for them through early treatment.