白细胞介素6受体基因多态性与日本人群慢性肾脏病的关联

Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals.

作者信息

Horibe Hideki, Fujimaki Tetsuo, Oguri Mitsutoshi, Kato Kimihiko, Matsuoka Reiko, Abe Shintaro, Tokoro Fumitaka, Arai Masazumi, Noda Toshiyuki, Watanabe Sachiro, Yamada Yoshiji

机构信息

Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.

出版信息

Nephrology (Carlton). 2015 Apr;20(4):273-8. doi: 10.1111/nep.12381.

DOI:10.1111/nep.12381

PMID:25524550

Abstract

AIM

Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs.

METHODS

The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60 mL min(-1) 1.73 m(-2) ] and 659 controls (eGFR of ≥90 mL min(-1) 1.73 m(-2) ). The genotypes for 29 polymorphisms of 28 candidate genes were determined.

RESULTS

The χ(2) test revealed that rs4845625 (T→C) of IL6R, rs4773144 (A→G) of COL4A1, rs9319428 (G→A) of FLT1, and rs46522 (T→C) of UBE2Z were significantly (P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P = 0.0065) greater and eGFR was significantly (P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype.

CONCLUSION

The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.

摘要

目的

通过全基因组关联研究（GWAS）在白种人群中已鉴定出多种赋予冠状动脉疾病（CAD）易感性的基因座和基因。本研究的目的是通过对GWAS的荟萃分析，检验慢性肾脏病（CKD）与先前鉴定为CAD易感基因座的29个多态性之间可能存在的关联。

方法

研究人群包括2247名日本个体，其中1588名患有CKD[估计肾小球滤过率（eGFR）<60 mL·min⁻¹·1.73 m⁻²]，659名对照者（eGFR≥90 mL·min⁻¹·1.73 m⁻²）。测定了28个候选基因的29个多态性的基因型。

结果

χ²检验显示，IL6R的rs4845625（T→C）、COL4A1的rs4773144（A→G）、FLT1的rs9319428（G→A）和UBE2Z的rs46522（T→C）与CKD显著相关（P<0.05）。在对年龄、性别、体重指数以及吸烟、高血压、糖尿病和血脂异常患病率进行校正的多变量逻辑回归分析中，IL6R的rs4845625（P = 0.0008；显性模型；优势比，1.49）、COL4A1的rs4773144（P = 0.0252；显性模型；优势比，1.28）和FLT1的rs9319428（P = 0.0260：加性模型；优势比，0.77）与CKD显著相关。IL6R的TC或CC基因型个体的血清肌酐浓度显著更高（P = 0.0065），eGFR显著更低（P = 0.0009）。