Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population

Abstract

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan® (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using χ2 tests and a Mantel–Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34–1.55), with an overall P = 1.85 × 10-23 for the rs2004640 T allele. The haplotype (rs2004640T–rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 × 10-16). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations.

Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

“…18 Since then, several additional studies have evaluated the association between IRF5 and SLE in Caucasian, [12][13][14]17,19 Korean 16 and Hispanic (Mexican) 15 populations, emphasizing the importance of this gene in SLE etiology. However, no studies have been reported to date in African Americans.…”

“…9 Interferon regulatory factor-5 (IRF5), a transcription factor, regulates the expression of IFN-a genes, 10,11 thus making it a good candidate gene for SLE susceptibility. Recent publications have reported a significant association between single nucleotide polymorphisms (SNPs) and haplotypes of IRF5 and SLE, both in familyand population-based studies of patients from multiple ethnicities [12][13][14][15][16][17][18][19][20][21] (including meta-analyses) 16 ; however, these studies have not examined African Americans.…”

“…28 There are even differences in levels of significance within association studies of IRF5 and SLE, such as with studies of Caucasian, 12,14,[17][18][19] Hispanic (Mexican) 15 and Asian subjects. 16 In this report, we evaluate genetic associations of IRF5 with SLE in independent studies (Oklahoma Medical Research Foundation (OMRF) and 'Cases of SLE' (CASSLE) based at the University of Alabama at Birmingham (UAB)) comprised of African-American and Caucasian patients and controls (n ¼ 4870). We replicate the previous associations of IRF5 with SLE found in multiple Caucasian populations and report novel findings of associations in African Americans.…”

Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: Support for a crucial role of intron 1 polymorphisms

“…For the meta-analysis of rs2004640, our data on Japanese subjects and previously published data on Korean subjects (14) were pooled using the DerSimonian-Laird method with the random effects model (22). Lack of heterogeneity between the 2 populations was examined using the Breslow-Day test of homogeneity.…”

“…Thus far, only 1 study of IRF5 polymorphisms in Asian populations has been published (14). In that examination of 4 SNPs, only 1 of them corresponded to the SNPs that define the Caucasian risk haplotype (14).…”