A Multicenter Allelic Analysis of Diffuse Idiopathic Skeletal Hyperostosis: Nature Versus Nurture?

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BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is an incompletely defined disease process with no known unifying pathophysiological mechanism.

OBJECTIVE: To our knowledge, no genetic studies have been performed in a North American population. To summarize genetic findings from previous studies and to comprehensively test for these associations in a novel and diverse, multi-institutional population.

METHODS: Cross-sectional, single nucleotide polymorphism (SNP) analysis was performed in 55 of 121 enrolled patients with DISH. Baseline demographic data were available on 100 patients. Based on allele selection from previous studies and related disease conditions, sequencing was performed on COL11A2, COL6A6, fibroblast growth factor 2 gene, LEMD3, TGFB1, and TLR1 genes and compared with global haplotype rates.

RESULTS: Consistent with previous studies, older age (mean 71 years), male sex predominance (80%), a high frequency of type 2 diabetes (54%), and renal disease (17%) were observed. Unique findings included high rates of tobacco use (11% currently smoking, 55% former smoker), a higher predominance of cervical DISH (70%) relative to other locations (30%), and an especially high rate of type 2 diabetes in patients with DISH and ossification of the posterior longitudinal ligament (100%) relative to DISH alone (100% vs 47%, P < .001). Compared with global allele rates, we found higher rates of SNPs in 5 of 9 tested genes (P < .05).

CONCLUSION: We identified 5 SNPs in patients with DISH that occurred more frequently than a global reference. We also identified novel environmental associations. We hypothesize that DISH represents a heterogeneous condition with both multiple genetic and environmental influences.

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ePub ahead of print