title: Mannose-binding lectin (MBL) codon 54 (rs1800450) polymorphism predisposes towards medium vessel vasculitis in patients with systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus. The exon1 variants at codon 52, 54, and 57 have been reported to augment the risk of SLE in different ethnic populations. Three hundred South Indian Tamil patients with SLE and 460 age-, sex-, and ethnicity-matched controls were genotyped for three polymorphisms at codon 52, 54, and 57 in exon1 of MBL gene by Taqman real-time PCR. The three polymorphisms in exon1 of MBL were observed not to confer risk of developing SLE. However, MBL codon 54 rs1800450 polymorphism was associated with the development of medium vessel vasculitis and gangrene (OR-2.29, CI 95% 1.08-4.83, p = 0.02), whereas, the ancestral allele G conferred protection (OR-0.44, CI 95% 0.21-0.93, p = 0.02). Genetic variants in the exon1 of MBL gene per se are not risk factors for SLE in South Indian Tamils. However, the association of codon 54 (rs1800450) with medium vessel vasculitis suggests that it may be a genetic modifier of clinical phenotype in SLE.
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India. vsnegi22@yahoo.co.in.
authors.forename: Vir Singh
authors.initials: VS
authors.lastname: Negi
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Panneer
authors.initials: P
authors.lastname: Devaraju
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Durga Prasanna
authors.initials: DP
authors.lastname: Misra
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Vikramraj K
authors.initials: VK
authors.lastname: Jain
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Jignesh Babulal
authors.initials: JB
authors.lastname: Usdadiya
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Antony
authors.affiliation: Genetic Services Unit, Department of Paediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Gulati
mesh_terms: D000328:Adult; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014657:Vasculitis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D003062:Codon; D037601:Mannose-Binding Lectin
keywords: Autoantibody; MBL gene polymorphism; Systemic lupus erythematosus; Taqman real time PCR; Vasculitis