Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus in southern chinese

Abstract

Objective. To investigate the predisposing role of major histocompatibility complex (MHC) genes to systemic lupus erythematosus (SLE) in a Chinese population.Methods. Polymorphism in the HLA-DRB, DQB, complement component C4, and 21-hydroxylase genes was analyzed by restriction fragment length polymorphism analysis and oligonucleotide probing of in vitrwamplified DNA from 88 Chinese patients with SLE and 69 matched control subjects.Results. HLA-DRwlS and DQwl were significantly more frequent in patients (corrected P < 0.006, relative risk 5.2), but none of the 9 sequence variants of DQwl were increased. The C4A gene deletion usually associated with SLE in Caucasoid and black patients Conclusion. Different MHC haplotypes predispose to lupus in Chinese than in other ethnic groups. Our data suggest that the susceptibility lies at, or telomeric to, the DR locus, and that DRwlS and C4 deletions may act synergistically in conferring disease susceptibility .Susceptibility to systemic lupus erythematosus (SLE) is associated with the polymorphic genes within the major histocompatibility complex (MHC). In particular, several reports have described increases in the frequencies of HLA-B8, DR2, DR3, and DQwl (la), as well as null alleles of C4A (2,3,5), in different lupus populations. A finding common to several ethnic groups is an increased risk conferred by a 30-kilobase DNA deletion in the MHC class 111 region, encornpassing the C4 gene and the 21-hydroxylase A (CYP2IA) pseudogene, which is usually linked with DR3 in white patients (6)(7)(8) and with DR2 or DR3 in black patients (9). This deletion, however, is not associated with SLE in all populations (10).To investigate the relative contributions of the MHC class I1 and class I11 genes to SLE and its clinical manifestations, we determined DR and DQ genotypes and MHC class 111 gene polymorphisms in a large series of lupus patients and controls of Southern Chinese origin. This population represents an ethnically well-defined and clinically well-characterized study group in which the lupus-susceptibility alleles can be compared with those in other ethnic groups.

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

“…[28][29][30][31][32][33][34] C4A*Q0 is also associated with SLE susceptibility in multiethnic Asian populations, including Japanese and Chinese. 35 This result has been replicated in Korean, 19 Japanese 36 and Chinese, 37 but also not in Chinese 16 and Malaysian. 38 However, C4A*Q0 is known to be in linkage disequilibrium with HLA-DR3.…”

Identification of a significant association of a single nucleotide polymorphism in TNXB with systemic lupus erythematosus in a Japanese population

“…In earlier days, the frequency of an 8.5 kb-HindIII band (corresponding to C4A gene deletion) was reported to be higher in SLE patients (20.5-24.5%) than in control individuals (7.9-12.9%) in the Caucasian population (Kemp et al 1987;Goldstein et al 1988;Reveille et al 1991;Hartung et al 1992), while in an AfroAmerican population, its frequencies were 14.5% in SLE patients and 3.7% in controls (Olsen et al 1989). On the other hand, this 8.5 kb-HindIII band itself was not observed in Japanese, Korean, or Chinese populations (Yamada et al 1990;Doherty et al 1992;Hong et al 1994), indicating that this particular allele was extremely rare or absent in Asian populations. Two basepair insertion mutations that would cause a premature stop codon in exon 30 of the C4A gene were reported in Caucasian SLE patients (Barba et al 1993;Lokki et al 1999), but we found such mutation in none of our SLE patients (data not shown).…”

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

“…Fronek et al (7) and Doherty et al (6) described an association with HLA-DR2 and SLE nephritis in Americans. Lupus nephritis has also been associated with the HLA-DR3, HLA-DR15 and HLA-DR16 alleles in different ethnic groups (6,7,28). There is no description in the literature of an association between HLA alleles and SLE hematologic involvement.…”

“…Some studies have observed an association with HLA alleles and cutaneous or cardiac involvement (6). In addition, most studies showed an association between HLA-DRB1*02 and DRB1*15 and lupus nephritis, although HLA alleles have rarely been associated with SLE renal histologic class (3,4,6,7). The association with HLA and SLE in children appears to be similar to that observed in adults, but clinical involvement, autoantibodies and renal histologic class frequencies are quite different in these two groups (8).…”

“…It is recognized that certain HLA alleles show stronger association with autoantibody repertories and clinical subsets than with SLE itself. Some studies have observed an association with HLA alleles and cutaneous or cardiac involvement (6). In addition, most studies showed an association between HLA-DRB1*02 and DRB1*15 and lupus nephritis, although HLA alleles have rarely been associated with SLE renal histologic class (3,4,6,7).…”