Human Fc gamma receptor IIA (FcγRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia

Abstract

SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.

<i>FcγRIIB </i>Gene Polymorphisms Are Associated with Disease Risk and Clinical Manifestations of Systemic Lupus Erythematosus in Koreans

“…Yun et al (2001) identified that FCGRIIA R131 homozygote was a major predisposing factor for SLE and LN, and H131/V176 was a protective allele combination in LN. However, FCGRIIA was not associated with Chinese (Yap et al 1999) and Japanese SLE (Hatta et al 1999;Sato et al 2001). FcγR IIB is the only inhibitory receptor with immunoreceptor tyrosine-based inhibitory motif, which inhibits activating signals in immune cells (Smith and Clatworthy 2010).…”

Genetics and Epigenetic in Systemic Lupus Erythematosus

“…Siriboonrit et al also found in a Japanese cohort that the R allele was significantly increased in patients with lupus nephritis (Siriboonrit, 2003). In various ethnic groups (Europeans, African Americans and Koreans), R131 (rs1801274) showed inconsistent association with susceptibility to SLE, lupus nephritis, or both (Duits, 1995;Yap, 1999;Chen, 2004;Salmon, 1996;Song, 1998). Ethnic differences, disease heterogeneity, genotyping error due to extensive sequence homology among FCGR genes and random fluctuations in small samples might explain these inconsistent associations.…”

“…FcγR3IIIA receptor contains ITAM on cell surfaces of natural killer (NK) cells, monocytes, and macrophages. Fc R3A alleles with differential affinity for IgG1 and IgG3 have also been shown to be associated with SLE patients from ethnically diverse groups (Yap, 1999). The nonsynonymous SNP, where valine (V158) of Fc RIIIA changes to phenylalanine (F158) (rs396991) was shown to reduce the IgG1-, IgG3-, and IgG4-binding capacity of the receptor compared to V/V homozygotes.…”

FcγRIIa Polymorphism in Systemic Lupus erythematosus

“…A similar study by Salmon et al [6] but involving only American Caucasians (262 SLE patients and 103 non-SLE controls), failed to replicate the findings of Duits et al [5] that FcγRIIa allotypes are a risk factor with pathophysiologic importance for development of lupus nephritis in Caucasian SLE patients. [12] et al [5] et al [6] et al [7] et al [7] et al [7] et al [8] et al [8] et al [9] et al [10] et al [11] The potential association of FcγRIIa allotypes with SLE in other racial groups was extended to include patients of Korean origin in a study by Song et al [9]. In this study from South Korea, there were 73 SLE patients and 64 non-SLE controls.…”

“…Compared to R131/R131 allotypes, H131/H131 allotypes were dominant in varying degrees in Chinese [7,11], Korean [9], Japanese [12] and Malay [11] ethnic groups reported so far. Overall, heterozygosity for H131/R131 was the most common allotype identified except in the Japanese study by Osborne et al [12] in which H131/H131 allotype was clearly predominant (61%) and in the Chinese study by Botto et al [7] in which the H131/H131 allotype was also clearly predominant (49%).…”