1998 Volvo Award winner in basic science studies - Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration

Study Design. A study in genetic epidemiology of disc degeneration, based o n lifetime exposure data, findings on magnetic resonance imaging, and genot yping of intragenic markers. Objectives. To pursue the potential correlation between common allelic vari ations in the vitamin D receptor locus and degeneration of the intervertebr al disc. Summary of Background Data. Familial aggregation has been observed in inter vertebral disc degeneration, but the relative significance of the genetic c omponent and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specif y a genetic component and increase our understanding of the etiopathogenesi s of disc degeneration. Methods. From the population-based Finnish Twin cohort, 85 pairs of male mo nozygotic twins were selected based on exposure to suspected risk factors f or disc degeneration. Interview data were gathered on relevant lifetime exp osures, and thoracic and lumbar disc degeneration was determined through qu antitative and qualitative assessments of signal intensity on magnetic reso nance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible association with disc degeneration. Quantitatively asse ssed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% wor se in men with the Taql tt genotype and 4.5% worse in men with the Tt genot ype, compared with signal intensity in men with the TT genotype (age-adjust ed P = 0.003). A similar pattern was found between disc signal intensity an d Fokl genotypes; men with the ff and Ff genotypes had mean signal intensit ies that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively ass essed signal intensity, bulging, and disc height were 4.0% and 6.9% worse i n men with Ff and ff genotypes, respectively, when compared with those in m en with the FF genotype (age-adjusted P = 0.029). Conclusion. Specific vitamin D receptor alleles were associated with interv ertebral disc degeneration as measured by T2-weighted signal intensity, dem onstrating for the first time, the existence of genetic susceptibility to t his progressive, age-related degenerative process.