Polymerase chain reaction based C4AQ0 and C4BQ0 genotyping: association with systemic lupus erythematosus in southwest Han Chinese.
OBJECTIVE
To investigate the association of complement C4 null genes (C4Q0, including C4AQ0 and C4BQ0) and C2 gene with systemic lupus erythematosus (SLE) in southwest Han Chinese; 136 patients with SLE and 174 matched controls were genotyped.


METHODS
C4 null genes were determined by a polymerase chain reaction (PCR) procedure with sequence specific primers (PCR-SSP). The 2 bp insertion in exon 29, which was previously identified in non-Chinese populations and caused defective C4A genes, was directly typed by sequencing the whole exon 29 using exon specific primers. The exon 6 of complement C2 was also sequenced in both the patients and controls.


RESULTS
The frequency of homozygous C4AQ0 allele was 12.5% (17/136) in patients with SLE compared with 1.1% (2/174) in controls (p<0.001, odds ratio (OR)=12.286, 95% confidence interval (95% CI) 2.786 to 54.170). There was no significant difference for homozygous C4BQ0 allele between patients with SLE and controls (p=0.699). Patients with the C4AQ0 gene had an increased risk of acquiring renal disorder, serositis, and anti-dsDNA antibodies compared with those without C4AQ0 (for renal disorder, p=0.018, OR=8.951, 95% CI 1.132 to 70.804; for serositis, p=0.011, OR 4.891, 95% CI 1.574 to 15.198; for anti-dsDNA, p=0.004, OR 7.630, 95%CI 1.636 to 35.584). None of the patients or controls had the 2 bp insertion in exon 29 of the C4 gene. The type I C2 deficiency was not detected in the 310 samples.


CONCLUSIONS
It is suggested that deficiency of C4A (not due to a 2 bp insertion in exon 29), but not C4B or C2, may be a risk factor for acquiring SLE in south west Han Chinese; this results in increased risk of renal disorder, serositis, and anti-dsDNA antibodies in patients with SLE. Racial differences seem to be relevant in susceptibility to SLE
Man
X-Y
XY
Laboratory of Molecular Evolution and Genome Diversity, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, People's Republic of China.
Luo
H-R
HR
Li
X-P
XP
Yao
Y-G
YG
Mao
C-Z
CZ
Zhang
Y-P
YP
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002681:China / Q000208:ethnology; D003175:Complement C2 / Q000235:genetics*; D003181:Complement C4 / Q000235:genetics*; D015934:Complement C4a / Q000235:genetics; D015935:Complement C4b / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods
D003175:Complement C2; D003181:Complement C4; D015934:Complement C4a; D015935:Complement C4b