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APOL1 基因变异与血液透析起始年龄年轻化相关。

Genetic variation in APOL1 associates with younger age at hemodialysis initiation.

机构信息

Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

出版信息

J Am Soc Nephrol. 2011 Nov;22(11):2091-7. doi: 10.1681/ASN.2010121234. Epub 2011 Oct 13.

Abstract

African Americans have a markedly higher incidence of ESRD compared with other racial groups. Two variants in the APOL1 gene, to date observed only among individuals of recent African ancestry, associate with increased risk for renal disease among African Americans. Here, we investigated whether these risk alleles also associate with age at initiation of chronic hemodialysis. We performed a cross-sectional study of 407 nondiabetic African Americans with ESRD who participated in the Accelerated Mortality on Renal Replacement (ArMORR) study, a prospective cohort of incident chronic hemodialysis patients. African Americans carrying two copies of the G1 risk allele initiated chronic hemodialysis at a mean age of 49.0 ± 14.9 years, which was significantly younger than both subjects with one copy of the G1 allele (55.9 ± 16.7 years; P = 0.014) and subjects without either risk allele (61.8 ± 17.1 years; P = 6.2 × 10(-7)). The association between the presence of the G1 allele and age at initiation of hemodialysis remained statistically significant after adjusting for sociodemographic and other potential confounders. We did not detect an association between the G2 risk allele and age at initiation of hemodialysis, but the sample size was limited. In conclusion, genetic variations in APOL1 identify African Americans that initiate chronic hemodialysis at a younger age. Early interventions to prevent progression of kidney disease may benefit this high-risk population.

摘要

非裔美国人的终末期肾病发病率明显高于其他种族。APOL1 基因的两个变体,迄今为止仅在具有近期非洲血统的个体中观察到,与非裔美国人的肾脏疾病风险增加相关。在这里,我们研究了这些风险等位基因是否也与慢性血液透析开始的年龄有关。我们对 407 名非糖尿病性终末期肾病的非裔美国人进行了横断面研究,这些患者参加了加速死亡率肾替代治疗(ArMORR)研究,这是一个新发病例慢性血液透析患者的前瞻性队列。携带两个 G1 风险等位基因的非裔美国人开始慢性血液透析的平均年龄为 49.0 ± 14.9 岁,明显低于携带一个 G1 等位基因的患者(55.9 ± 16.7 岁;P = 0.014)和没有任何风险等位基因的患者(61.8 ± 17.1 岁;P = 6.2×10(-7))。在调整了社会人口统计学和其他潜在混杂因素后,携带 G1 等位基因与开始血液透析的年龄之间的关联仍然具有统计学意义。我们没有发现 G2 风险等位基因与开始血液透析的年龄之间存在关联,但样本量有限。总之,APOL1 中的遗传变异可识别出开始慢性血液透析的非裔美国人年龄较小。早期干预以防止肾脏疾病进展可能使这一高危人群受益。

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