Vitamin D receptor gene FokI polymorphism in Egyptian children and adolescents with SLE: A case-control study

Abstract

Background Childhood-onset systemic lupus erythematosus (cSLE) is a lifelong autoimmune disorder. The vitamin D receptor (VDR) gene is a potential candidate gene for cSLE susceptibility. In this study, we aimed to investigate the FokI polymorphism in the VDR gene in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a genetic marker for cSLE susceptibility or disease activity and we also measured the serum level of 25-hydroxyvitamin D [25(OH) D] to assess its relation to such polymorphism. Methods This was a case-control study, which included 300 patients with cSLE and 300 age, sex, and ethnicity-matched healthy controls. All participants were genotyped for the VDR gene FokI (rs2228570) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum [25(OH) D] levels were measured by enzyme-linked immunosorbent assay (ELISA). Results The VDR FokI FF genotype and F allele were overrepresented among cSLE patients compared with the controls, [odds ratio (OR) = 2.7; 95% confidence interval (CI): 1.6-4.4 for the FF genotype; p = 0.000; and OR = 1.6; 95% CI: 1.27-2.05 for the F allele; p = 0.000, respectively]. We found a significant association between VDR FokI FF genotype with lupus nephritis (OR: 4.8; 95% CI: 2.2-10.6; p = 0.002); and high disease activity index score ( p = 0.01). Conclusions The FokI polymorphism in the VDR gene may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, the FF genotype constituted a risk factor for the development of lupus nephritis and was associated with low serum [25(OH) D] levels as well as higher disease activity index score among studied patients with cSLE.

Association between circulating 25‐hydroxyvitamin D and systemic lupus erythematosus: A systematic review and meta‐analysis

“…Ultimately, 19 studies were included in our meta‐analysis (Figure ). Sixteen studies compared circulating 25(OH)D levels between SLE patients and healthy controls (Table ); seven Studies provided the information about the deficiency, insufficiency, sufficiency of vitamin D in both SLE patients and healthy controls (Table ); 6 studies explored the correlations between disease activity of SLE and 25(OH)D levels (Table ). The NOS scores of included studies ranged from 6 to 8 stars, indicating each of the studies had high methodological quality (Table ).…”

“…Sixteen articles with 17 individual studies reported the circulating 25(OH)D levels of 1434 SLE patients and 1533 healthy controls. Compared with healthy controls, SLE patients had significantly lower 25(OH)D levels (pooled SMD = −1.63, 95% CI: −2.51 to −0.76), and significant heterogeneity was identified among these studies ( I 2 = 98.9%, P < .001) (Figure ).…”

“…Five studies reported the information about vitamin D deficiency in 747 SLE patients and 980 healthy controls. A significant association was detected between vitamin D deficiency and elevated SLE risk (pooled OR = 4.37, 95% CI :1.49 to 12.84, I 2 = 94.0%, Figure ).…”

“…Five studies including 747 SLE patients and 980 healthy controls elucidated the influence of vitamin D insufficiency on the risk of SLE. There was a pooled OR of 0.52 (95% CI: 0.22 to 1.26, I 2 = 91.0%, Figure ) between SLE patients and healthy controls, suggesting that vitamin D insufficiency could slightly decrease (not significantly) the risk of SLE.…”

“…The associations between vitamin D sufficiency and SLE risk were reported in seven studies with 953 SLE patients and 1181 healthy controls. The pooled results reveled that vitamin D sufficiency could significantly reduce the risk of SLE (pooled OR = 0.31, 95% CI: 0.15 to 0.63, I 2 = 88.3%, Figure ).…”