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Lupus Sci Med. 2016 Nov 14;3(1):e000145. eCollection 2016.

CR1 exon variants are associated with lowered CR1 expression and increased susceptibility to SLE in a Plasmodium falciparum endemic population.

Author information

1
Infectious Disease Biology Group, Institute of Life Sciences, Bhubaneswar, Odisha, India; Centre for Life Sciences, Central University of Jharkhand, Brambe, Ranchi, India.
2
Infectious Disease Biology Group , Institute of Life Sciences , Bhubaneswar, Odisha , India.
3
Infectious Disease Biology Group, Institute of Life Sciences, Bhubaneswar, Odisha, India; Department of Medicine, S.C.B. Medical College, Cuttack, Odisha, India.

Abstract

BACKGROUND:

Complement receptor 1 (CR1) plays an important role in immune complex clearance by opsonisation and possibly protects subjects from development of autoantibodies. Lower CR1 expression has been associated with susceptibility to systemic lupus erythematosus (SLE). In contrast, subjects displaying lower CR1 expression are protected against severe manifestations of falciparum malaria. This study is the first of its kind to investigate the association of CR1 variants with development of SLE in a P. falciparum endemic population from Odisha, India.

METHODS:

CR1 polymorphisms (intron 27 (A>T), exon 22 (A>G) and exon 33 (G>C)) were typed by PCR and restriction length polymorphism in 297 cases of female patients with SLE and 300 age-matched and sex-matched healthy controls from malaria endemic areas in Odisha, India. CR1 expression on monocytes was quantified by flow cytometry.

RESULTS:

The homozygous mutants of CR1 exon 22 (GG) and exon 33 (GG) and their minor alleles were associated with susceptibility to SLE. Furthermore, patients with SLE who harboured the GG genotype of the exon 33 polymorphism had a 3.12-fold higher chance of developing lupus nephritis. CR1 exon (22 and 33) variants were associated with lowered CR1 expression on monocytes in patients with SLE and in healthy controls. Patients with lupus nephritis showed significantly diminished CR1 expression than those without renal involvement (p=0.01).

CONCLUSIONS:

The results of the present study demonstrate that common CR1 exon variants are associated with diminished CR1 expression on monocytes and increased susceptibility to development of SLE and lupus nephritis in a malaria endemic area.

KEYWORDS:

Complement receptor 1; Gene Polymorphism; Plasmodium falciparum malaria; Predisposition; Systemic Lupus Erythematosus

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