Common Genetic Variants in the Chromogranin A Promoter Are Associated with Renal Injury in IGA Nephropathy Patients with Malignant Hypertension

Abstract

The present study aimed to investigate whether genetic variants in the chromogranin A (CHGA) promoter were associated with malignant hypertension (MHT) and renal functional damage. The polymorphisms of CHGA promoter in 39 patients with malignant hypertension secondary to idiopathic IgA nephropathy (IgAN-MHT), 23 patients with primary malignant hypertension and 63 controls were genotyped by sequencing. Four diploid genotypes with minor allele frequencies of approximately ≥10% for individual CHGA SNP loci or haplotypes were compared among the patient with IgAN-MHT, primary MHT and healthy control. Polymorphisms and haplotypes of CHGA promoter were not associated with primary MHT and IgAN-MHT. Within 39 IgAN-MHT patients whose clinical and histological data were available, patients carrying −415TT genotype tended to present with higher serum creatinine (Scr) level than those carrying −415TC/CC genotype (636.94 ± 524.07 μmol/L vs 277.84 ± 196.39 μmol/L, P = 0.014). Consistent with this statistic, we found the haplotype-specific score value of haplotype ATC was 2.25046 (p = 0.024), and by permutation testing, the empirical p value was 0.014. The present study suggested the genetic variants in the chromogranin A promoter may not involve in the onset of malignant hypertension, but the variants might play a role in the renal dysfunction in patients with IgAN-MHT.