Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers

Mihailo I Stjepanovic; Violeta Mihailovic-Vucinic; Vesna Spasovski; Jelena Milin-Lazovic; Vesna Skodric-Trifunovic; Sanja Stankovic; Marina Andjelkovic; Jovana Komazec; Ana Momcilovic; Milena Santric-Milicevic; Sonja Pavlovic

doi:10.5114/aoms.2018.79682

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers

Arch Med Sci. 2019 Sep;15(5):1138-1146. doi: 10.5114/aoms.2018.79682. Epub 2018 Nov 23.

Authors

Affiliations

¹ Clinic of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia.
² Medical Faculty, University of Belgrade, Belgrade, Serbia.
³ Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
⁴ Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia.
⁵ Institute of Social Medicine, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Abstract

Introduction: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients.

Material and methods: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method.

Results: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients.

Conclusions: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.

Keywords: 25(OH)D; CYP27B1; CYP2R1; DBP; VDR; single nucleotide polymorphisms.