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 FcgR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcγRIIA) occurs in two allelic forms. The allele FcγRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcγRIIA-H131 has a higher capacity for hIgG2 compared to FcγRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcγRIIA 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 (w² 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 FcγRIIA-H131 in the ethnic groups studied.

Keywords

Chinese Fc gamma receptor IIA (FcγRIIA)Malays systemic lupus erythematosus (SLE)

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References

Kotzin BL . Systemic lupus erythematosus . Cell 1996; 85: 303–306 .

Bachelot C , Safroy R , Gandrille S et al. Role of Fc gamma RIIA gene polymorphism in human platelet activation by monoclonal antibodies . Thromb Haemost 1995; 74: 1557–1563 .

van de Winkel JG , Capel PJ . Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications . Immunol Today 1993; 14: 215–221 .

Kimberly RP , Salmon JE , Edberg JC . Receptors for immunoglobulin G. Molecular diversity and implications for disease . Arthritis Rheum 1995; 38: 306–314 .

Deo YM , Graziano RF , Repp R et al. Clinical significance of IgG Fc receptors and Fc gamma R-directed immunotherapies . Immunol Today 1997; 18: 127–135 .

Ravetch JV . Fc receptors: rubor redux . Cell 1994; 78: 553–560 .

Warmerdam PA , van de Winkel JG , Gosselin EJ et al. Molecular basis for a polymorphism of human Fc gamma receptor II (CD32) . J Exp Med 1990; 172: 19–25 .

Gmelig-Meyling FHJ , Bootsma H , Derksen RHWM et al. IgG Fc receptor IIa (CD32) polymorphism in SLE: Skewed allotype distribution among patients with renal disease . Ahtritis Rheum 1994; 37: S167-S167 (abstract 149).

Duits AJ , Bootsma H , Derksen RH et al. Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients . Arthritis Rheum 1995; 38: 1832–1836 .

10.

Salmon JE , Millard S , Schachter LA et al. Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans . J Clin Invest 1996; 97: 1348–1354 .

11.

Song YW , Han CW , Kang SW et al. Abnormal distribution of Fc gamma receptor type IIa polymorphisms in Korean patients with systemic lupus erythematosus . Arthritis Rheum 1998; 41: 421–426 .

12.

Botto M , Theodoridis E , Thompson EM et al. Fc gamma RIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease . Clin Exp Immunol 1996; 104: 264–268 .

13.

Smyth LJ , Snowden N , Carthy D et al. Fc gamma RIIa polymorphism in systemic lupus erythematosus . Ann Rheum Dis 1997; 56: 744–746 .

14.

Manger K , Repp R , Spriewald BM et al. Fc gamma receptor IIa polymorphism in Caucasian patients with systemic lupus erythematosus: association with clinical symptoms . Arthritis Rheum 1998; 41: 1181–1189 .

15.

Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter] . Arthritis Rheum 1997; 40: 1725-1725 .

16.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

17.

Miller SA , Dykes DD , Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells . Nucleic Acids Res 1988; 16: 1215-1215 .

18.

Osborne JM , ChackoGW , BrandtJT etal. Ethnic variation infrequency of an allelic polymorphism of human Fc gamma RIIA determined with allele specific oligonucleotide probes . J Immunol Methods 1994; 173: 207–217 .

19.

Satoh T , Kobayashi M , Kaneda M et al. Genotypical classification of neutrophil Fc gamma receptor III by polymerase chain reaction-single-strand conformation polymorphism . Blood 1994; 83: 3312–3315 .

20.

Jiang XM , Arepally G , Poncz M et al. Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED) . J Immunol Methods 1996; 199: 55–59 .

21.

Clynes R , Dumitru C , Ravetch JV . Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis . Science 1998; 279: 1052–1054 .

22.

Takai T . Multiple loss of effector cell functions in FcR gamma deficient mice . Int Rev Immunol 1996; 13: 369–381 .

23.

Carroll MC . The lupus paradox [news; comment] . Nat Genet 1998; 19: 3–4 .

24.

Veggeberg S . Lupus: Complement cascade, Fc receptors or both? [news] . Mol Med Today 1998; 4: 184-184 .

25.

Denomme G , Ryan G , Fernandes B . The FcgRIIA-H131 allotype is overexpressed in infants with ABO hemolytic disease of the newborn . Blood 1997; 90 (Suppl 1): S472a-S472a (abstract 2100).