title: C4A gene deletion and HLA associations in black Americans with systemic lupus erythematosus.
abstract: In North America and European Caucasoids with systemic lupus erythematosus (SLE) there is an increased frequency of a C4A, CYP21A gene deletion, largely associated with the HLA-B8,DR3,C4A*QO extended haplotype. There have been no consistent HLA associations reported for SLE in blacks, although an increased frequency of serologically determined C4A null alleles has been reported in two studies. We studied 79 black American SLE patients and 68 black controls by restriction fragment length polymorphism analysis to determine if a C4A gene deletion was a genetic risk factor for SLE. Moreover, the nature of the deletion and any HLA phenotypic associations were sought. Nineteen of 79 (24%) patients compared to 5 of 68 (7.4%) controls had a phenotypic C4A,CYP21A gene deletion (P = .005; RR = 4). A homozygous deletion in four patients gave a genotypic frequency of 23/158 (14.5%) SLE patients vs 5/136 (3.7%) controls (P = .001; RR = 4.5). The deletion was associated with HLA-DR2 (P = .03) and HLA-DR3 (P = .03). Moreover, all subjects with the deletion had HLA-DR2 or DR3 (P = 7.7 x 10(-6). HLA-B44 was also associated with the deletion (P = .02), and eight of the nine HLA-B44 positives also carried HLA-DR2. HLA-B8 approached significance (P = .08) and was always accompanied by HLA-DR3. Finally, this black population demonstrated a unique C4B gene size polymorphism with 80% C4B "short" as compared to the 40% C4B "short" frequency reported in whites. We conclude that a large C4A,CYP21A gene deletion, particularly associated with the HLA-B44, -DR2, and -DR3 alleles, is the strongest genetic risk factor thus far identified for SLE susceptibility in black Americans. Furthermore, the unique preponderance of the C4B "short" gene form may be a factor in the actual formation of the deletion.
authors.affiliation: Department of Internal Medicine, University of Texas Health Science Center Houston 77225.
authors.forename: M L
authors.initials: ML
authors.lastname: Olsen
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
authors.forename: F C
authors.initials: FC
authors.lastname: Arnett
authors.forename: M
authors.initials: M
authors.lastname: Duvic
authors.forename: M
authors.initials: M
authors.lastname: Pollack
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
mesh_terms: D044383:Black People / Q000235:genetics*; D002872:Chromosome Deletion; D003181:Complement C4 / Q000172:deficiency / Q000235:genetics*; D015934:Complement C4a; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D014481:United States; D001741:Black or African American
chemical_list: D003181:Complement C4; D006680:HLA Antigens; D015934:Complement C4a