Genotype Triad for HOTAIR rs10783618, LINC-ROR rs1942347, and MALAT1 rs3200401 as Molecular Markers in Systemic Lupus Erythematous

Nesreen M Ismail; Eman A Toraih; Amany I Almars; Essam Al Ageeli; Manal S Fawzy; Shymaa Ahmed Maher

doi:10.3390/diagnostics12051197

Genotype Triad for HOTAIR rs10783618, LINC-ROR rs1942347, and MALAT1 rs3200401 as Molecular Markers in Systemic Lupus Erythematous

Diagnostics (Basel). 2022 May 11;12(5):1197. doi: 10.3390/diagnostics12051197.

Authors

Nesreen M Ismail¹, Eman A Toraih^{2

3}, Amany I Almars⁴, Essam Al Ageeli⁵, Manal S Fawzy⁶, Shymaa Ahmed Maher^{7

8}

Affiliations

¹ Department of Rheumatology and Rehabilitation, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
² Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.
³ Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Ismailia 41522, Egypt.
⁴ Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia.
⁶ Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 1321, Saudi Arabia.
⁷ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
⁸ Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.

Abstract

Accumulating evidence supports the implication of long non-coding RNAs (lncRNAs) in autoimmune diseases, including systemic lupus erythematosus (SLE). LncRNA variants could impact the development and/or outcome of the disease with variable diagnostic/prognostic utility in the clinic. We aimed to explore the contribution of HOTAIR (rs10783618), LINC-ROR (rs1942347), and MALAT1 (rs3200401) variants to SLE susceptibility and/or severity in 163 SLE patients and age-/sex-matched controls using real-time TaqMan allelic discrimination PCR. HOTAIR rs10783618*C/C was associated with a 77% increased risk of SLE (OR = 1.77, 95%CI = 1.09−2.87, p = 0.020) under the recessive model. Similarly, MALAT1 rs3200401*T/T carriers were three times more likely to develop SLE (OR = 2.89, 95%CI = 1.42−5.90) under the recessive model. While the rs3200401*T/C genotype was associated with a 49−57% decreased risk of SLE under codominant (OR = 0.51, 95%CI = 0.31−0.82, p < 0.001) and over-dominant (OR = 0.43, 95%CI = 0.27−0.68, p < 0.001) models. LINC-ROR rs1942347*A/A patients were more likely to have a positive family history of SLE. At the same time, HOTAIR rs10783618*C/C was associated with a higher frequency of arthritis (p = 0.001) and the presence of oral ulcers (p = 0.002), while patients carrying rs10783618*T/T genotype were more likely to develop hair loss (p < 0.001), weight loss (p = 0.001), and neurological symptoms (p = 0.003). In conclusion, the studied lncRNAs, HOTAIR, and MALAT1 gene polymorphisms confer susceptibility for SLE, providing a potential theoretical basis for their clinical translation in SLE disease.

Keywords: HOTAIR; LINC-ROR; MALAT1; SLE; long non-coding RNAs; lupus nephritis; single nucleotide polymorphism.

Grants and funding

The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number “IF_2020_NBU_220”.