Sistemik Lupus Eritematozus’lu Hastalarda C-Reaktif Proteindeki Tek Nükleotid Polimorfizmlerin Araştırılması

Abstract

Amaç: Bu çalışmada, sistemik lupus eritematozus (SLE) hastalarında C-reaktif protein (CRP) gen polimorfizmlerinin sıklığı ve bu polimorfizmlerin hastalığın klinik ve laboratuvar özellikleriyle ilişkisi araştırıldı. Gereç ve Yöntemler: Üçüncü basamak hastanede romatoloji bölümüne başvuran SLE hastaları çalışmaya dahil edildi. Romatolojik ve sistemik hastalık öyküsü olmayan yaş-cinsiyet eşleştirilmiş sağlıklı bireyler kontrol grubu olarak seçildi. CRP genindeki tek nükleotid polimorfizmleri (rs1130864, rs1205 ve rs1800947) her iki grupta da genotiplendirildi. Rs1205 (CC/CT/TT), rs1130864 (CC/CT/TT) ve rs1800947 (CC/GC) için genotip sıklıkları hastalar ve kontrol grupları arasında karşılaştırıldı. SLE hastalarında polimorfizmlerin varlığı ve hastalığın klinik belirtileri arasındaki ilişki incelendi. Bulgular: Bu çalışmaya 74 SLE hastası ve 72 sağlıklı kontrol dahil edildi. SLE grubunda genotip sıklıkları şu şekildeydi: Rs1205: CC, % 43,7 (n=31); CT, % 46,5 (n=33); ve TT, % 9,9 (n=7); rs1130864: CC, % 54,3 (n=38); CT, % 42,9 (n=30); ve TT, % 2,9 (n=2); rs1800947: GC, % 93,1 (n=67). SLE hastaları ve kontroller arasında CRP genindeki tek nükleotid polimorfizmleri sıklıklarında istatistiksel olarak anlamlı bir fark gözlenmedi. Rs1205 CC genotipi, SLE hastalarında daha yüksek oral ülser sıklığı ve daha düşük kompleman seviyeleri ile ilişkilendirildi. Sonuç: CRP geni tek nükleotid polimorfizmleri ile SLE yatkınlığı arasında bir ilişki saptanmamış olsa da, bu polimorfizmler SLE hastalarının belirli klinik özelliklerini etkileyebilir.

Keywords

• Sistemik lupus eritematozus
• c-reaktif protein
• biomarker
• tek nükleotid polimorfizmleri
• genetik polimorfizm

INVESTIGATION OF SINGLE NUCLEOTIDE POLYMORPHISMS IN C-REACTIVE PROTEIN IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

Objective: This study investigated the frequency of C-reactive protein (CRP) gene polymorphisms and their association with clinical and laboratory features in systemic lupus erythematosus (SLE). Material and Methods: A cohort of SLE patients presenting to the tertiary rheumatology department center was enrolled. Agesex matched healthy individuals without a history of rheumatologic/systemic disease served as controls. Single nucleotide polymorphisms (SNPs) within the CRP gene (rs1130864, rs1205, and rs1800947) were genotyped in both groups. The genotype frequencies for rs1205 (CC/CT/TT), rs1130864 (CC/CT/TT), and rs1800947 (CC/GC) were compared between SLE patients and controls. Associations between SNPs and clinical manifestations of SLE patients were assessed. Results: This study included 74 SLE patients and 72 healthy controls. In the SLE group, genotype frequencies were as follows: Rs1205: CC, 43.7 % (n=31); CT, 46.5 % (n=33); and TT, 9.9 % (n=7); rs1130864: CC, 54.3 % (n=38); CT, 42.9 % (n=30); and TT, 2.9 % (n=2); rs1800947: GC, 93.1 % (n=67). No statistically significant differences in SNP frequencies were observed between SLE patients and controls. The rs1205 CC genotype was associated with higher prevalence of oral ulcers and lower complement levels in SLE patients. Conclusion: While no association with disease susceptibility was identified, CRP gene polymorphisms may influence specific clinical features of SLE patients.

Keywords

• Systemic lupus erythematosus
• c-reactive protein
• biomarker
• single nucleotide polymorphism
• genetic polymorphism

Thanks

Dear Editor, 26/03/2025 We would like to submit our research article “Single Nucleotid polymorphisims in C-reactive protein are associated with oral ulcers in patients with Systemic lupus eritematosus” for consideration to be published in  Journal of Kırıkkale University Faculty of Medicine. Genetic factors implicated in SLE demonstrate considerable variability in their association with disease susceptibility, severity, and across diverse populations, leading to inconsistent findings. We aimed to investigate the rate of CRP gene polymorphisms in a Turkish SLE patient cohort and to determine their relationship with clinical manifestations of the disease. The study included 74 SLE patients and 72 healthy controls. In the SLE group, genotype frequencies were as follows: rs1205: CC, 43.7% (n=31); CT, 46.5% (n=33); and TT, 9.9% (n=7); rs1130864: CC, 54.3% (n=38); CT, 42.9% (n=30); and TT, 2.9% (n=2); rs1800947: GC, 93.1% (n=67). No statistically significant differences in SNP frequencies were observed between SLE patients and controls. However, in SLE patients, the rs1205 CC genotype was associated with a higher prevalence of oral ulcers and lower complement levels.We did not identify susceptibility to SLE, but we highlighted that CRP gene polymorphisms may influence specific clinical features of SLE within the Turkish population. The manuscript has not been and will not be submitted to any other journal while it is under consideration by  Journal of Kırıkkale University Faculty of Medicine. Each individual named as an author meets the journal’s criteria for authorship. Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript. None of the authors received financial support, and no potential conflicts of interest exist for this work. Authors agree to bear the applicable publication charges if the manuscript is accepted for publication. Kindest regards, Güllü Sandal UZUN, MD e-mail: [e-mail]

References

1. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-939.
2. Barber MRW, Drenkard C, Falasinnu T, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17(9):515-532.
3. Pesqueda-Cendejas K, Parra-Rojas I, Campos-López B, et al. Association of c.+677 C>T(rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic and disease risk in systemic lupus erythematosus patients: A cross-sectional study. Lupus. 2024;33(9):918-928.
4. Pesqueda-Cendejas K, Parra-Rojas I, Meza-Meza MR, et al. Association of - 717 A > G(rs2794521) CRP pollymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients. Clin Rheumatol. 2023;42(3):761-772.
5. Deafen D, Escalante A, Weinrib L, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis & Rheumatism. 1992;35(3):311-318.
6. Carlton VE, Ireland JS, Useche F, Faham M. Functional single nucleotide polymorphism-based association studies. Hum Genomics. 2006;2(6):391-402.
7. Cui Y, Sheng Y, Zhang X. Genetic susceptibility to SLE: recent progress from GWAS. J Autoimmun. 2013;41:25-33.
8. Rhodes B, Vyse TJ. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford). 2008;47(11):1603-1611.

9. Bell SA, Faust H, Schmid A, Meurer M. Autoantibodies to C-reactive protein (CRP) and other acute-phase proteins in systemic autoimmune diseases. Clin Exp Immunol. 1998;113(3):327-332.
10. Kapur S, Gauri LA, Singh U, et al. Association of CRP Haplotypes in Rheumatoid Arthritis and their Correlation with Severity of the Disease. J Assoc Physicians India. 2022;70(1):11-12
11. Palomino-Morales R, Vazquez-Rodriguez TR, Miranda-Filloy JA, Martin J, Gonzalez-Gay MA. C-reactive protein gene polymorphisms in biopsy-proven giant cell arteritis from Northwestern Spain. J Rheumatol. 2009;36(2):341-346.
12. Kim HA, Chun HY, Kim SH, Park HS, Suh CH. C-reactive protein gene polymorphisms in disease susceptibility and clinical manifestations of Korean systemic lupus erythematosus. J Rheumatol. 2009;36(10):2238-2243.
13. Rhodes B, Meek J, Whittaker JC, Vyse TJ. Quantification of the genetic component of basal C-reactive protein expression in SLE nuclear families. Ann Hum Genet. 2008;72(Pt 5):611-620.
14. Jönsen A, Gunnarsson I, Gullstrand B, et al. Association between SLE nephritis and polymorphic variants of the CRP and FcgammaRIIIa genes. Rheumatology (Oxford). 2007;46(9):1417-1421.
15. Russell AI, Cunninghame Graham DS, Shepherd C, et al. Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet. 1 2004;13(1):137-147.
16. Atisha-Fregoso Y, Lima G, Carrillo-Maravilla E, et al. C-reactive protein (CRP) polymorphisms and haplotypes are associated with SLE susceptibility and activity but not with serum CRP levels in Mexican population. Clin Rheumatol. 2018;37(7):1817-1824.
17. Delongui F, Lozovoy MAB, Iriyoda TMV, et al. C-reactive protein +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels. Clin Rheumatol. 2017;36(8):1779-1788.
18. Szalai AJ, Alarcón GS, Calvo-Alén J, et al. Systemic lupus erythematosus in a multiethnic US Cohort (LUMINA). XXX: association between C-reactive protein (CRP) gene polymorphisms and vascular events. Rheumatology (Oxford). 2005;44(7):864-868.
19. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686.
20. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288-291.
21. Shih PB, Manzi S, Shaw P, et al. Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations. J Rheumatol. 2008;35(11):2171-2178.
22. Enocsson H, Sjöwall C, Kastbom A, et al. Association of serum C-reactive protein levels with lupus disease activity in the absence of measurable interferon-α and a C-reactive protein gene variant. Arthritis Rheumatol. 2014;66(6):1568-1573.
23. Li QY, Lv JM, Liu XL, Li HY, Yu F. Association of C-reactive protein and complement factor H gene polymorphisms with risk of lupus nephritis in Chinese population. World J Clin Cases. 6 2023;11(13):2934-2944.