Role of PAX2 gene polymorphisms in Henoch–Schonlein purpura nephritis

Objective:  To investigate the distribution of polymorphisms in the PAX2 gene in children with Henoch–Schonlein purpura with and without nephritis (HSPN and HSP, respectively), with particular attention to the relationship between PAX2 gene polymorphisms and the development of kidney pathology.

Methods:  Genomic DNA was extracted from the peripheral leukocytes of 39 HSPN patients, 23 HSP patients without nephritis and 100 normal children, and three known single nucleotide polymorphisms (SNP), including 1410C>T, 1521A>C and 1544C>T in exon 8 and exon 9 of the PAX2 gene were studied as the candidate polymorphisms. The above two exons were amplified, the polymerase chain reaction (PCR) products were detected by denatured high-pressure liquid chromatography and direct DNA sequencing was performed for sequences with abnormal elution peaks.

Results:  In all samples confirmed by direct sequencing, we identified two SNP, which present as complete linkage haplotype 1410C>T + 1521A>C, in exon 8. We did not identify any SNP in exon 9. The frequency of the PAX2 heterozygous genotype 1410CT/1521AC in the HSPN group (28.20%) was significantly higher than in the HSP without HSPN group (4.35%) or in the control group (12.00%) (P < 0.05). The odds ratio (OR) values for HSPN and HSP were 6.05 and 2.62, respectively, and the 95% confidence intervals (CI) were 1.23–29.78 and 1.09–6.30, respectively. However, no differences in the frequency distribution was found between the HSP without nephritis and normal groups. Furthermore, there was no significant correlation between the polymorphism and clinical manifestation or kidney pathology in the HSPN group (P > 0.05).

Conclusion:  The 1410CT/1521AC PAX2 genotype does not increase susceptibility for HSP, but is likely to increase the susceptibility of kidney involvement, resulting in a HSPN diagnosis.