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The effect of IL-4 and MTHFR gene variants in ankylosing spondylitis

Auswirkungen von IL-4 - und MTHFR-Genvarianten auf die ankylosierende Spondylitis

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Abstract

Purpose

Ankylosing Spondylitis (AS) is a chronic inflammatory rheumatic disease that characteristically affects the sacroiliac joints and the spine. The exact pathogenesis of AS remains poorly understood, but genetic factors play a key role in disease development. Several genes have been consistently associated with susceptibility to AS. This study was conducted in Turkish AS patients to determine the frequency of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and interleukin-4 (IL-4) gene 70 bp variable number of tandem repeats (VNTR) variants, as well as their association with clinical characteristics.

Methods

Genomic DNA obtained from 272 persons (122 AS patients and 150 healthy controls) was used in this study. Genomic DNA was isolated and genotyped using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MTHFR C677T and IL-4 70 bp VNTR gene variants, which were determined using specific PCR primers.

Results

There was statistically significant difference between the groups with respect to MTHFR genotype distribution (p = 0.02) and allele frequencies (p < 0.001). When we examined MTHFR and IL-4 genotype frequencies according to clinical characteristics, we found an association between the homozygous MTHFR TT genotype and ocular involvement, although this did not reach statistical significance (p = 0.02). However, we did not find any difference between the groups with respect to IL-4 genotype distribution or allele frequencies and clinical characteristics (p > 0.05).

Conclusion

Our findings suggest that there is an association of the MTHFR gene C677T polymorphism with the susceptibility of a person for development of AS. However, the IL-4 gene is not associated with AS within the same population.

Zusammenfassung

Ziel

Die ankylosierende Spondylitis (AS) ist eine chronisch entzündliche rheumatische Erkrankung, die typischerweise die Sakroiliakalgelenke und die Wirbelsäule betrifft. Die Pathogenese der AS ist bis heute nicht genau geklärt, jedoch spielen genetische Faktoren eine wesentliche Rolle bei ihrer Entstehung. Durchgängig wurden mehrere Gene mit der Anfälligkeit für eine AS in Verbindung gebracht. Die vorliegende Studie an türkischen AS-Patienten wurde mit dem Ziel durchgeführt, die Häufigkeit des Methylentetrahydrofolatreduktase(MTHFR)-Gens C677T und von 70-bp-Variable-Number-of-Tandem-Repeats(VNTR)-Varianten des Interleukin-4(IL-4)-Gens sowie ihren Zusammenhang mit klinischen Merkmalen zu ermitteln.

Methoden

In dieser Studie wurde genomische DNA von 272 Personen (122 AS-Patienten und 150 gesunde Kontrollen) eingesetzt. Isoliert und genotypisiert wurde die genomische DNA unter Verwendung eines polymerasekettenreaktions(PCR)-basierten Restriktionsfragmentlängenpolymorphismus(RFLP)-Assays für die Genvarianten MTHFR-C677T und IL-4-70-bp-VNTR, die mittels spezifischer PCR-Primer bestimmt wurden.

Ergebnisse

Es bestanden statistisch signifikante Unterschiede zwischen den Gruppen in Hinblick auf die MTHFR-Genotypverteilung (p = 0,02) und -Allelfrequenz (p < 0,001). Bei der Untersuchung der MTHFR- und IL-4-Genotyphäufigkeit gemäß klinischen Merkmalen stellte sich ein Zusammenhang zwischen homozygotem MTHFR-TT-Genotyp und Augenbeteiligung heraus, allerdings erreichte dieser keine statistische Signifikanz (p = 0,02). Es fand sich jedoch kein Unterschied zwischen den Gruppen in Bezug auf die IL-4-Genotypverteilung und -Allelfrequenz und klinische Merkmale (p > 0,05).

Schlussfolgerung

Den vorliegenden Befunden zufolge gibt es einen Zusammenhang zwischen dem MTHFR-Gen-C677T-Polymorphismus und der Anfälligkeit einer Person für die Entwicklung einer AS. Das IL-4-Gen ist innerhalb derselben Population jedoch nicht mit AS vergesellschaftet.

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Compliance with ethical guidelines

Conflict of interest. S. Yigit, A. Inanir, S. Tural, B. Filiz and A. Tekcan state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Medical Biology, Gaziosmanpaşa University, Tokat, Turkey

    S. Yigit PhD

  2. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Gaziosmanpaşa University, Tokat, Turkey

    A. Inanir MD & B. Filiz MD

  3. Faculty of Medicine, Department of Medical, Section of Medical Genetics, Ondokuz Mayis University, Samsun, Turkey

    S. Tural PhD

  4. Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

    A. Tekcan PhD

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  1. S. Yigit PhD
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  2. A. Inanir MD
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  4. B. Filiz MD
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  5. A. Tekcan PhD
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Correspondence to A. Tekcan PhD.

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Yigit, S., Inanir, A., Tural, S. et al. The effect of IL-4 and MTHFR gene variants in ankylosing spondylitis. Z. Rheumatol. 74, 60–66 (2015). https://doi.org/10.1007/s00393-014-1403-2

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