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        Association of MMP-9 C-1562T polymorphism with risk of Henoch-Schönlein purpura nephritis in children of southeast China

        Jinwen Xu,Liping Zhao,Hongxia Zhou,Tingting Ge,Lin Zhang 한국유전학회 2017 Genes & Genomics Vol.39 No.4

        Henoch-Schönlein purpura nephritis (HSPN) is the most prevalent vasculitis in childhood worldwide. Although the etiology of HSPN is not yet fully elucidated, it is believed to be closely related with infections and genetic predispositions. In this study, a cohort of children from southeast China, including 108 healthy controls and 184 patients were involved in. We scanned the promoter region and the whole gene for genetic variations. A C/T transition located in the promoter region of MMP-9 gene, C-1562T was identified. Subjects were genotyped by using SNaPshot sequencing and the frequencies of CC, CT and TT genotypes were 43, 33 and 24% in patients and 53, 37 and 10% in healthy controls. Allele distribution was found to be in Hardy–Weinberg equilibrium (P = 0.17). Association analysis revealed that the polymorphism was significantly related with HSPN risk (P < 0.05) and T allele was shown to be a risk factor (P = 0.003, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.13–2.34). Additionally, we measured the serum MMP-9 concentration and quantified the mRNA expression. Results showed that an elevated protein level was observed in patients compared with controls in both ELISA (P = 0.0029, 136.5 μg/L vs. 103.9 μg/L) and Western blot assays. Furthermore, we also detected 1.93-fold increase in the mRNA transcription in patients carrying homozygous TT genotype, indicating enhanced promoter activity caused by the polymorphism. Based on the incidence risk, a cut-off value of serum MMP-9 served as HSPN diagnosis was suggested at 155 μg/L. Conclusively, our findings suggested that MMP-9 polymorphism was significantly associated with HSPN susceptibility, and C-1562T T allele contributed to HSPN development.

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