维生素D受体基因多态性对尿毒症甲状旁腺功能的影响

Association between vitamin D receptor gene polymorphism and severity of secondary hyperparathyroidism in uremic patients

目的 :评价维生素D受体 (VDR)基因多态性对尿毒症患者继发性甲状旁腺功能亢进 (SHPT)的影响。方法 :10 6例尿毒症维持性血液透析患者采用聚合酶链反应———限制性片段长度 (PCR RFLP)方法分析VDR基因Apa Ⅰ位点多态性 ,有ApaⅠ酶切位点的等位基因为a ,无酶切位点者定为A。 结果 :10 6例患者VDR基因ApaⅠ多态性频率分别为AA 17%、Aa 5 4 7%、aa 2 8 3%。aa基因组患者血清iPTH水平 (339 8± 35 7 4ng/L)明显高于AA基因组 (15 1 9± 16 7 3ng/L ,P <0 0 5 )和Aa基因组患者 (191 5± 16 9 8ng/L ,P <0 0 5 )。aa基因组患者骨钙素水平 (36 2± 5 6 0 μg/L)明显高于AA基因组 (9 2± 6 1μg/L ,P <0 0 5 )和Aa基因组患者 (15 3± 2 1 6 μg/L ,P <0 0 5 )。三组间血钙、磷、镁均无明显差别 ,但aa基因组降钙素水平明显低于Aa基因组 (30 2± 17 6ng/Lvs 73 2± 6 8 3ng/L ,P <0 0 1)。 结论 :a等位基因患者易产生严重的SHPT。

Objective:To assess the association between vitamin D receptor(VDR)gene polymorphism and the severity of secondary hyperparathyroidism in uremic patients. Methodology:VDR gene polymorphisms were determined by the restriction Apa I enzyme and polymerase chain reaction in 106 patients with maintenance hemodialysis.Digested allele was designated as “a” and the undigested alleles as “A”.Serum intact PTH(iPTH),osteocalcin and calcitonin were measured with RIA. Results:The frequencies for Apa I polymorphism were 17% for AA,54 7% for Aa,and 28 3% for aa genotypes.The iPTH level in patientswith aa genotype was significantly higher than that in patients with AA and Aa genotypes(339 8±357 4 ng/L vs 151 9±167 3 ng/L and 191 5±169 8 ng/L,all P <0 05).The average ostocalcin concentration in patients with aa genotype was significantly higher than those of patients with AA or Aa genotypes(36 2±56 0 μg/L vs 9 2±6 1 μg/L and 15 3±21 6 μg/L,all P <0 05).The average serum concentration of calcitonin in patients with aa genotype was significantly lower than that in patients with Aa genotype(30 2±17 6 ng/L vs 73 2±68 3 ng/L).No significant difference in electrolytes,age,sex,dialysis duration or percentage of diabetic nephropathy was found among the patients with the three genotypes. Conclusion:The results suggested the existance of an association between aa genotype and severe secondary hyperparathyroidism in uremic patients.