FokI polymorphism in the vitamin D receptor gene (VDR) and its association with lumbar spine pathologies in the Italian population: a case-control study.

Alterations in vitamin D homeostasis, mainly involving its nuclear receptor (VDR), could have a role in the pathophysiology of the spine. The association between VDR polymorphisms and spine disorders has been analyzed in different ethnic groups, focusing on the functional FokI polymorphism. However, so far, inconsistent findings were reported. The aims of this study were to evaluate, in the Italian white population, the VDR FokI polymorphism frequencies distribution in subjects with clearly defined lumbar spinal pathologies compared to asymptomatic controls and to analyze the interplay of genetic and conventional risk factors. Using a case-control design, 267 patients with spinal disorders and 220 asymptomatic controls were enrolled, evaluating their exposition to putative risk factors. Patients' clinical assessment was performed by Magnetic Resonance Imaging. FokI polymorphism (rs2228570) was detected by PCR-RFLP. Genotypes were designated by a lowercase letter (f allele, T nucleotide) for the presence of the restriction site and by a capital letter (F allele, C nucleotide) for its absence. Family history, higher age and BMI, exposure to vibration, physical job demand, smoking habit and lower practice of leisure physical activity were associated with spinal disorders. The FF genotype and F allele represented approximately 2-fold risk factors to develop discopathies and/or osteochondrosis concomitant with disc herniation, while f allele was protective. In conclusion, the link we observed between VDR FokI variants and specific lumbar spine pathologies suggests that spinal tissue degeneration is influenced by the genetic background. Future studies should evaluate the signaling pathways involving alterations in VDR and influencing the development and/or progression of spine disorders

Characteristics of the subjects recruited and influence of risk factors of lumbar spine pathologies.

1<p>5 patients had missing information about intensity of physical demand at work, thus a total of 262 data were available. Physical job demand score used: 0 = sedentary; 1 = light; 2 = medium; 3 = heavy.</p>2<p>1 patient had missing information about leisure physical activity per week, thus a total of 266 data were available.</p>3<p>Orthopedic conditions included: osteoarthrosis, hip, knee and hand osteoarthritis, and osteoporosis.</p><p>Subgroup 1 = patients with disc herniation alone; Subgroup 2 = patients with discopathies and/or osteochondrosis associated with disc herniation; Subgroup 3 = patients with discopathies and/or osteochondrosis without herniation; Subgroup 4 = patients with stenosis and/or spondylolisthesis.</p><p>Only significant P≤0.05 were indicated.</p

Association of lumbar spine pathologies and <i>VDR</i> FokI alleles.

<p>Subgroup 1 = patients with disc herniation alone; Subgroup 2 = patients with discopathies and/or osteochondrosis associated with disc herniation; Subgroup 3 = patients with discopathies and/or osteochondrosis without herniation; Subgroup 4 = patients with stenosis and/or spondylolisthesis. Subgroup A, Subgroup 1 grouped with Subgroup 2 (i.e. all hernia cases with or without concomitant additional conditions); Subgroup B, Subgroup 2 grouped with Subgroup 3; Subgroup C, all discopathies cases with or without concomitant disc herniation; Subgroup D, all osteochondrosis cases with or without concomitant disc herniation.</p>1<p>Adjusted OR: multivariate analysis, OR adjusted for age, BMI, family history, smoke, physical job demand and exposure to vibrations.</p><p>Only significant P≤0.05 were indicated.</p

Patient’s clinical assessment and classification in subgroups.

<p>a) Subgroup 1, patients with disc herniation only. b) Subgroup 2, patients with discopathies and/or osteochondrosis associated with disc herniation. c) Subgroup 3, patients with discopathies and/or osteochondrosis, without disc herniation, d–f) Subgroup 4, patients with stenosis (d), spondylolisthesis (e) or both (f). White arrows indicate the characteristic pathological features of each subgroup.</p

<i>VDR</i> FokI genotypes and alleles in controls and cases.

1<p>Adjusted OR: multivariate analysis, OR adjusted for age, BMI, family history, smoke, physical job demand and exposure to vibrations.</p

Association of lumbar spine pathologies and <i>VDR</i> BsmI, ApaI, and TaqI combined genotypes.

<p>Association of lumbar spine pathologies and <i>VDR</i> BsmI, ApaI, and TaqI combined genotypes.</p

Estimated frequencies of <i>VDR</i> BsmI, ApaI, and TaqI haplotypes.

<p>Estimated frequencies of <i>VDR</i> BsmI, ApaI, and TaqI haplotypes.</p

LD plots (r²) are shown for all subjects (a), controls (b) and cases (c).

<p>LD plots (r²) are shown for all subjects (a), controls (b) and cases (c).</p

Characteristics of the study subjects and comparison of conventional and non-genetic risk factors of lumbar spine pathologies between controls and all cases or subgroups.

<p>Characteristics of the study subjects and comparison of conventional and non-genetic risk factors of lumbar spine pathologies between controls and all cases or subgroups.</p

Association of lumbar spine pathologies and <i>VDR</i> BsmI, ApaI, and TaqI alleles.

<p>Association of lumbar spine pathologies and <i>VDR</i> BsmI, ApaI, and TaqI alleles.</p