ROMATOİD ARTRİT’TE FC GAMA RESEPTÖR IIIA V/158/F GEN POLİMORFİZMİNİN SIKLIĞININ ARAŞTIRILMASI VE HASTA KLİNİK VE LABORATUAR BULGULARIYLA KARŞILAŞTIRILMASI

Year 2018, Volume: 81 Issue: 4, 139 - 144, 01.12.2018

Ali Murat Sedef , Suzan Dikci Eren Erken

Abstract

DOI: 10.26650/IUITFD.426162

Amaç: Romatoid Artrit (RA), nedeni
bilinmeyen, esas olarak periferik eklemleri progresif olarak tutan kronik
multisistemik bir hastalıktır. Hümoral ve hücresel immün yanıtları arasında bir
bağ olan, IgG‘ nin Fc reseptörleri otoimün hastalıkların etyoloji ve
patogenezinde oldukça ilgi çekmektedir. Geniş genetik varyasyon sergileyen bu
bölge Romatoid artrit de dahil olmak üzere çeşitli kronik inflamatuvar
hastalıklara yatkınlık ile ilişkilidir. Bu çalışmasında Romatoid Artrit‘ te
FcγRIIIA V158F gen polimorfizminin sıklığının araştırılması ve hasta klinik ve
laboratuar bulgularıyla karşılastırılması amaçlanmıştır.

Gereç ve Yöntem: Çukurova Üniversitesi Tıp
Fakültesi Romatoloji Bilim Dalı polikliniğine Nisan 2010-Haziran 2011 tarihleri
arasında başvuran ve Amerikan Romatizma Derneği‘ nin tanı kriterlerine göre RA
tanısı almış 105 RA‘lı hasta ve 110 sağlıklı kontrol çalışmaya dahil edildi.
Hasta ve kontrollerden öyküsünde diyabet, tiroid fonksiyon bozuklukları,
geçirilmiş veya mevcut kalp hastalıkları, malignite, nörolojik hastalıklar ile
kronik inflamatvuar hastalıklardan bir ya da daha fazlası olanlar çalışma dışı
bırakıldı. RA‘ lı hastaların hastalıkla ilgili semptomları, sistemik hastalık
varlığı, ilaç kullanımı, hastalık süreleri ve aile öyküsü sorgulandı. Tüm
olgulara genel fizik muayene ve romatolojik muayeneleri yapıldı ve rutin
laboratuvar tetkikleri ile CRP, RF, ESR, ANA, Anti-DNA düzeyleri istendi. Hasta
grubu ARA‘nın fonksiyonel sınıflandırması kullanılarak evrelere ayrıldı. Alınan
kan örneklerinde real time PCR yöntemi ile FcγRIIIA V158F gen polimorfizmleri
araştırıldı.

Bulgular: Hasta ve kontrol grubunun Fc γ
RIIIA gen polimorfizm dağılımları arasında anlamlı fark saptanmadı (p=0,106).
Hastaların tanı aldıkları yaş dağılımları ile gen polimorfizmi arasında anlamlı
fark saptanmadı (p=0,919). Hastaların cinsiyet dağılımlarına göre de gen
polimorfizmi açısından anlamlı fark saptanmadı (p=0,552). Hastalığın klinik
bulgularından olan akciğer ve göz tutulumları, romatoid nodül varlığı ile gen
polimorfizmi arasında ilişki saptanmadı. RF ve ANA sonuçları ile gen
polimorfizmi arasında da anlamlı fark saptanmadı (p=0,625, p=0,716). Hastaların
anti-CCP sonuçları ile gen polimorfizmi arasında anlamlı fark saptanmadı
(p=0,136).

Sonuç: Çalışmamızda RA patogenezi ile Fc γ
RIIIA 158 gen polimorfizmi arasında anlamlı bir ilişki saptanmamıştır. 

Keywords

FcγRIIIA gen polimorfizmi, romatoid artrit

INVESTIGATION OF THE FREQUENCY OF FC GAMMA RECEPTOR IIIA V/158/F GENE POLYMORPHISM AND COMPARISON OF CLINICAL AND LABORATORY FINDINGS IN RHEUMATOID ARTHRITIS (RA)

Abstract

DOI: 10.26650/IUITFD.426162

Objective: Rheumatoid Arthritis (RA) is a
chronic multisystem disease with unknown etiology that progressively affects
peripheral joints. Receptors, which serve as links between humoral and cellular
immune responses, recognize the Fc region of immunoglobulin G (FcR) and have
become the focus of many research studies concerning the etiology and
pathogenesis of autoimmune diseases. This region displays extensive genetic
variation, which has been associated with susceptibility to various chronic
inflammatory disorders including RA. This study aimed to investigate the
frequency of the FcγRIIIA V158F genetic polymorphism and compare clinical and
laboratory findings in RA.

Materials and Methods: Between April 2010
and June 2011, 105 patients, who had been diagnosed with RA according to the
American Rheumatology Association (ARA) diagnostic criteria, were admitted to
the Cukurova University Department of Rheumatology outpatient clinic and 110
healthy controls were included in this study. Patient groups were divided into
stages using the ARA functional classification. The FcγRIIIA V158F gene polymorphism
of patients was investigated from blood samples using the real-time Polymerase
Chain Reaction (PCR) method.

Results: There was no significant
difference in the distribution of the FcγRIIIA polymorphism between patients
and controls (p=.106). There were no significant differences between the
distribution of age at diagnosis of patients with the gene polymorphism
(p=.919) or in the gene polymorphism (p=.552). No association was found between
the gene polymorphism and clinical signs of disease such as eye involvement and
the presence of rheumatoid nodules. There was also no significant association
between the gene polymorphism with rheumatoid factor, anticyclic citrullinated
peptide, and antinuclear antibodies (p=.625, p=.136, p=.716, respectively).

Conclusion: In our study, no significant
relationship was found between the FcγRIIIA V158F gene polymorphism and the
pathogenesis of RA.

Keywords

FcγRIIIA V158F gene polymorphism, rheumatoid arthritis

References

• References:Reference1: Rothschild BM, Turner KR, DeLuca MA. Symmetrical erosive peripheral polyarthritis in the Late Archaic Period of Alabama. Science 1988; 241:1498.Reference2: Spector TD. Rheumatoid arthritis. Rheum Dis Clin North Am 1990; 16:513.Reference3: Peschken CA, Esdaile JM. Rheumatic diseases in North America's indigenous peoples. Semin Arthritis Rheum 1999; 28:368.Reference4: Kleinau S. The impact of Fc receptors on the development of autoimmune diseases. Curr Pharm Des 2003; 9:1861–70.Reference5: Dijstelbloem HM, van de Winkel JG, Kallenberg CG. Inflammation in autoimmunity: receptors for IgG revisited. Trends Immunology 2001; 22:510–6.Reference6: Anderson R. "Manipulation of cell surface macromolecules by flaviviruses". Adv. Virus Res. 2003; 59:229–74. doi:10.1016/S0065-3527(03)59007-8. PMID 14696331.Reference7: Yuan H, Pan HF, Li LH, Feng JB, Li WX, et al. Meta analysis on the association between FcgammaRIIa-R/H131 polymorphisms and systemic lupus erythematosus. Mol Biol Rep 2009; 36(5):1053–1058.Reference8: Carcao MD, Blanchette VS, Wakefield CD, Stephens D, Ellis J, et al. Fc gamma receptor IIa and IIIa polymorphisms in childhood immune thrombocytopenic purpura. Br J Haematol 2003; 120(1):135–141Reference9: Schrohenloher RE, Bridges SL, Koopman WJ Jr. Rheumatoid Factor. In: Kopman WJ (ed). Arthritis and Allied Conditions. 13th ed, Pennsylvania, Williams and Wilkins,1109-1130, 1997.Reference10: Hochberg MC, Chang RW, Dwosh I. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid artritis. Arthritis Rheum 1992; 35 (5):498-502.Reference11:Morgan AW, Keyte VH, Babbage SJ et al. Fc_RIIIA-158V and rheumatoid arthritis: a confirmation study. Rheumatology 2003; 42:528–33. Reference12. Hepburn AL, Mason JC, Davies KA. Expression of Fcgamma and complement receptors on peripheral blood monocytes in systemic lupus erythematosus and rheumatoid arthritis. Rheumatology 2004; 43:547–54. Reference13. Blom AB, Radstake TR, Holthuysen AE et al. Increased expression of Fcgamma receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor alpha and matrix metalloproteinase. Arthritis Rheum 2003; 48:1002–14. Reference14. Wijngaarden S, van Roon JA, Bijlsma JW, van de Winkel JG, Lafeber FP. Fc_ receptor expression levels on monocytes are elevated in rheumatoid arthritis patients with high erythrocyte sedimentation rate who do not use anti-rheumatic drugs. Rheumatology 2003; 42:681–8. Reference15. Abrahams VM, Cambridge G, Lydyard PM, Edwards JC. Induction of tumor necrosis factor alpha production by adhered human monocytes: a key role for Fc_ receptor type IIIa in rheumatoid arthritis. Arthritis Rheum 2000; 43:608–16. Reference16. A. Kastbom, A. Ahmadi, P. Söderkvist and T. Skogh. The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increased susceptibility and severity in male patients (the Swedish TIRA project). Rheumatology 2005; 44:1294-1298.58Reference17. Ann W Morgan, Jennifer H Barrett, Bridget Griffiths, Deepak Subramanian, Jim I Robinson, Viki H Keyte, Manir Ali, Elizabeth A Jones, Robert W Old, Frederique Ponchel, Arthur W Boylston, R Deva Situnayake, Alexander F Markham, Paul Emery and John D Isaacs. Analysis of Fc receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B. Arthritis Research & Therapy 2006; 8:R5 (doi:10.1186/ar1847)Reference18: Nieto A, Cáliz R, Pascual M, Matarán L, García S, Martín J. Involvement of Fcgamma receptor IIIA genotypes in susceptibility to rheumatoid arthritis. Arthritis Rheumatology 2002 Feb; 46(2):556-9.Reference19: Morgan AW, Griffiths B, Ponchel F, Montague BM, Ali M, Gardner PP, Gooi HC, Situnayake RD, Markham AF, Emery P, Isaacs JD. Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups. Arthritis Rheum. 2002 Feb; 46(2):556-9.Reference20: Thabet MM, Huizinga TWJ, Marques RB, Stoeken-Rijsbergen R, Bakker AM, Kurreeman FA, White SJ, Toes R. The contribution of Fc gamma receptor IIIA gene 158V/F polymorphism and copy number variation to the risk of ACPA positive rheumatoid arthritis, Ann Rheum Dis 2008; 10:1136.