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Fulltext The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review

Sakthiswary R, Raymond AA

PLoS One, 2013;8(1):e55275.
PMID: 23383135 DOI: 10.1371/journal.pone.0055275

BACKGROUND: Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.
METHODS: THE FOLLOWING DATABASES WERE SEARCHED: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms "lupus", "systemic lupus erythematosus", "SLE and "vitamin D". We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.
RESULTS: A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.
CONCLUSION: There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.

Matched MeSH terms: Lupus Erythematosus, Systemic/metabolism*
Fulltext Insight into gene polymorphisms involved in toll-like receptor/interferon signalling pathways for systemic lupus erythematosus in South East Asia

Chai HC, Chua KH, Lim SK, Phipps ME

J Immunol Res, 2014;2014:529167.
PMID: 24741605 DOI: 10.1155/2014/529167

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P = 0.014; OR = 1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001.
Study site: University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Lupus Erythematosus, Systemic/metabolism*
Fulltext Steroid-induced osteoporosis--a cause for concern?

Tan TT, Lau IS, Kong NC, Zainal AG

Malays J Pathol, 1997 Jun;19(1):27-33.
PMID: 10879239
Matched MeSH terms: Lupus Erythematosus, Systemic/metabolism
Fulltext Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM

Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.

Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
PMID: 24608226 DOI: 10.1093/hmg/ddu106

Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.

Matched MeSH terms: Lupus Erythematosus, Systemic/metabolism
Fulltext Dietary calcium and bone mineral density in premenopausal women with systemic lupus erythematosus

Chong HC, Chee SS, Goh EM, Chow SK, Yeap SS

Clin Rheumatol, 2007 Feb;26(2):182-5.
PMID: 16565892 DOI: 10.1007/s10067-006-0258-6

The primary objective of this study was to determine the relationship between dietary calcium intake and bone mineral density (BMD) in premenopausal women with systemic lupus erythematosus (SLE) on corticosteroids (CS). The secondary aim was to identify other risk factors for osteoporosis in these patients. A cross-sectional sample of patients attending the SLE Clinic at a teaching hospital was recruited. BMD was measured using dual-energy X-ray absorptiometry. Daily dietary calcium intake was assessed using a structured validated food frequency questionnaire, in which patients were asked to estimate their food intake based on their recent 2-month dietary habits. Sixty subjects were recruited with a mean age of 33.70+/-8.46 years. The median duration of CS use was 5.5 years (range 0.08-24). The median cumulative dose of steroids was 17.21 g (range 0.16-91.37). The median daily dietary calcium intake was 483 mg (range 78-2101). There was no significant correlation between calcium intake and BMD, even after correcting for CS use. There were also no correlations between BMD and the duration of SLE, cumulative CS use, duration of CS use, smoking, alcohol intake, and SLE disease activity index score. Twenty-eight (46.7%) patients had normal BMD, 28 (46.7%) had osteopenia, and four (6.6%) had osteoporosis. Duration of SLE significantly correlated with cumulative CS dosage. In conclusion, 6.7% of these Asian premenopausal SLE women had osteoporosis and only 46.7% had normal BMD. Daily dietary calcium intake did not correlate with BMD.
Study site: SLE clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Lupus Erythematosus, Systemic/metabolism*