背景:捷克共和国的5期慢性肾病(CKD5)比大多数欧洲国家更普遍,遗传易感性是潜在的牵连。
方法:在一组1489名CKD5肾移植患者中(93%具有完整的临床特征;平均年龄52.0岁,37%的女性)和2559名健康对照(平均年龄49.0岁,51%的女性),我们检测了6个APOL1单核苷酸多态性(rs73885319,rs71785313,rs13056427,rs136147,rs10854688和rs9610473)和1个新检测到的55个核苷酸的插入/缺失多态性。
结果:rs73885319和rs71785313变体在捷克高加索人群中是单态的。所检查的三个SNP(rs13056427,rs136147和rs9610473)的基因型频率在患者和对照组中几乎相同(所有P值都在0.39和0.91之间)。rs10854688的次要纯合子在患者之间(13.2%)比对照组(10.7%)更常见(OR[95%CI];1.32[1.08-1.64];P<0.01)。CKD5患者新检测到的55bpAPOL1缺失的患病率显着升高(3.0%vs.1.7%;OR[95%CI];1.80[1.16-2.80];P<0.01)与对照组相比。某些个体APOL1单倍型的频率在患者和对照组之间是临界差异。
结论:我们发现APOL1基因rs10854688SNP与捷克高加索人群终末期肾病之间存在关联。在新检测到的APOL1插入/缺失多态性与CKD5之间的决定性关联之前,需要进一步的独立研究。
BACKGROUND: With stage 5 chronic kidney disease (CKD5) more prevalent in the Czech Republic than in most European countries, genetic susceptibility is potentially implicated.
METHODS: In a group of 1489 CKD5 kidney transplantation patients (93% with complete clinical characteristics; mean age 52.0 years, 37% females) and 2559 healthy controls (mean age 49.0 years, 51% females), we examined the prevalence of six APOL1 SNPs (rs73885319, rs71785313, rs13056427, rs136147, rs10854688 and rs9610473) and one newly detected 55-nucleotide insertion/deletion polymorphism.
RESULTS: The rs73885319 and rs71785313 variants were monomorphic in the Czech Caucasian population. Genotype frequencies of the three SNPs examined (rs13056427, rs136147 and rs9610473) were almost identical in patients and controls (all P values were between 0.39 and 0.91). Minor homozygotes of rs10854688 were more common between the patients (13.2%) than in controls (10.7%) (OR [95% CI]; 1.32 [1.08-1.64]; P < 0.01). Prevalence of the newly detected 55-bp APOL1 deletion was significantly higher in CKD5 patients (3.0% vs. 1.7%; OR [95% CI]; 1.80 [1.16-2.80]; P < 0.01) compared to controls. Frequencies of some individual APOL1 haplotypes were borderline different between patients and controls.
CONCLUSIONS: We found an association between rs10854688 SNP within the APOL1 gene and end-stage renal disease in the Czech Caucasian population. Further independent studies are required before a conclusive association between the newly detected APOL1 insertion/deletion polymorphism and CKD5 can be confirmed.