线粒体DNA D环区域的单核苷酸多态性与慢性肾病患者的发病年龄

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease.

作者信息

Bai Yaling, Guo Zhanjun, Xu Jinsheng, Zhang Junxia, Cui Liwen, Zhang Huiran, Zhang Shenglei, Ai Xiaolu

机构信息

Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

Departments of Gastroenterology and Hepatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

出版信息

Chin Med J (Engl). 2014;127(17):3088-91.

PMID:25189950

Abstract

BACKGROUND

The mitochondrial displacement loop (D-loop) accumulates mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). We previously identified disease risk-associated SNPs in the D-loop of chronic kidney disease (CKD) patients; in this study, we investigated the association of age-at-onset and D-loop SNPs in CKD patients.

METHODS

The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. The age-at-onset curve of the CKD patients was calculated using the Kaplan-Meier method at each SNP site, and compared using the log-rank test.

RESULTS

The mean age of 119 CKD patients was (55.6±14.2) years, and 56.3% were males. The mean estimated glomerular filtration rate (eGFR) was (81.2±12.4) ml×min(-1)×1.73 m(-2), with 79.8% (n = 95) of patients having an eGFR <60 ml×min(-1)×1.73 m(-2). All participants had an eGFR >30 ml×min(-1)×1.73 m(-2). The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients. The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site (P = 0.010).

CONCLUSIONS

Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.

摘要

背景

线粒体置换环（D环）积累突变和单核苷酸多态性（SNP）的频率高于线粒体DNA（mtDNA）的其他区域。我们之前在慢性肾脏病（CKD）患者的D环中鉴定出与疾病风险相关的SNP；在本研究中，我们调查了CKD患者发病年龄与D环SNP的关联。

方法

对2002年至2008年期间在河北医科大学第四医院就诊的119例CKD患者的mtDNA的D环区域进行测序。使用Kaplan-Meier方法在每个SNP位点计算CKD患者的发病年龄曲线，并使用对数秩检验进行比较。

结果

119例CKD患者的平均年龄为（55.6±14.2）岁，男性占56.3%。平均估计肾小球滤过率（eGFR）为（81.2±12.4）ml×min⁻¹×1.73 m⁻²，79.8%（n = 95）的患者eGFR<60 ml×min⁻¹×1.73 m⁻²。所有参与者的eGFR>30 ml×min⁻¹×1.73 m⁻²。吸烟的CKD患者的发病年龄显著低于不吸烟的CKD患者。使用对数秩检验确定核苷酸150C/T的SNP位点与发病年龄的关联。在150 SNP位点，携带次要等位基因T基因型的患者的发病年龄显著低于携带C基因型的患者（P = 0.010）。