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Open Access Research

Sirtuin1 single nucleotide polymorphism (A2191G) is a diagnostic marker for vibration-induced white finger disease

Susanne Voelter-Mahlknecht12*, Bernd Rossbach1, Christina Schleithoff3, Christian L Dransfeld3, Stephan Letzel1 and Ulrich Mahlknecht3

Author Affiliations

1 Institute of Occupational, Social and Environmental Health, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany

2 Institute of Occupational Medicine, Social Medicine and Health Services Research, University of Tuebingen, Wilhelmstrasse 27, D-72074, Tuebingen, Germany

3 Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Research Center Saarland, University Medical Center, D-66421, Homburg/Saar, Germany

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Clinical Epigenetics 2012, 4:18  doi:10.1186/1868-7083-4-18

Published: 1 October 2012

Abstract

Background

Vibration-induced white finger disease (VWF), also known as hand-arm vibration syndrome, is a secondary form of Raynaud’s disease, affecting the blood vessels and nerves. So far, little is known about the pathogenesisof the disease. VWF is associated with an episodic reduction in peripheral blood flow. Sirtuin 1, a class III histone deacetylase, has been described to regulate the endothelium dependent vasodilation by targeting endothelial nitric oxide synthase. We assessed Sirt1single nucleotide polymorphisms in patients with VWF to further elucidate the role of sirtuin 1 in the pathogenesis of VWF.

Methods

Peripheral blood samples were obtained from 74 patients with VWF (male 93.2%, female 6.8%, median age 53 years) and from 317 healthy volunteers (gender equally distributed, below 30 years of age). Genomic DNA was extracted from peripheral blood mononuclear cells and screened for potential Sirt1single nucleotide polymorphisms. Four putative genetic polymorphisms out of 113 within the Sirt1 genomic region (NCBI Gene Reference: NM_012238.3) were assessed. Allelic discrimination was performed by TaqMan-polymerasechainreaction-based allele-specific genotyping single nucleotide polymorphism assays.

Results

Sirt1single nucleotide polymorphism A2191G (Assay C_25611590_10, rs35224060) was identified within Sirt1 exon 9 (amino acid position 731, Ile → Val), with differing allelic frequencies in the VWF population (A/A: 70.5%, A/G: 29.5%, G/G: 0%) and the control population (A/A: 99.7%, A/G: 0.3%, G/G: 0.5%), with significance levels of P < 0.001 (Mann–Whitney U test (two-tailed) P <0.001; F-exact t-test and Chi-square test with Yates correction (all two-tailed): P <0.0001). The heterogeneous A/G genotype in base pair position 2191 is significantly overrepresented in the VWF patient population when compared with healthy controls.

Conclusion

We identified theSirt1A2191Gsingle nucleotide polymorphism as a diagnostic marker for VWF.

Keywords:
Epigenetics; Hand-arm vibration syndrome (HAVS); Sirtuins; Vibration-induced white finger disease (VWF)