Renal Division of Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People's Republic of China.
Ren Fail. 2010 Jan;32(1):41-6. doi: 10.3109/08860220903377597.
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 >or=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 micromol/L vs 277.84 +/- 196.39 micromol/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.
本研究旨在探讨嗜铬粒蛋白 A (CHGA) 启动子的遗传变异是否与恶性高血压 (MHT) 和肾功能损害有关。通过测序对 39 例特发性 IgA 肾病继发恶性高血压 (IgAN-MHT) 患者、23 例原发性恶性高血压患者和 63 例对照者的 CHGA 启动子多态性进行基因分型。比较 IgAN-MHT、原发性 MHT 和健康对照组中个体 CHGA SNP 或单体型的次要等位基因频率 >or=10%的四个二倍体型基因型。CHGA 启动子的多态性和单体型与原发性 MHT 和 IgAN-MHT 无关。在 39 例临床和组织学资料完整的 IgAN-MHT 患者中，携带-415TT 基因型的患者血清肌酐 (Scr) 水平高于携带-415TC/CC 基因型的患者 (636.94 +/- 524.07 micromol/L vs 277.84 +/- 196.39 micromol/L, P = 0.014)。与这一统计结果一致，我们发现单体型 ATC 的单体型特异性评分值为 2.25046 (p = 0.024)，通过置换检验，经验 p 值为 0.014。本研究提示嗜铬粒蛋白 A 启动子的遗传变异可能与恶性高血压的发病无关，但变异可能在 IgAN-MHT 患者的肾功能障碍中起作用。
