Renin gene rs1464816 polymorphism contributes to chronic kidney disease progression in ADPKD

Autor: Bhaskar V.K.S. Lakkakula, Gnanasambandan Ramanathan, Ramprasad Elumalai, Soundararajan Periyasamy
Rok vydání: 2016
Předmět:
tag-SNPs
Adult
Male
0301 basic medicine
Oncology
medicine.medical_specialty
Linkage disequilibrium
Genotype
Haploview
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Autosomal dominant polycystic kidney disease
urologic and male genital diseases
Polymorphism
Single Nucleotide
REN gene
03 medical and health sciences
0302 clinical medicine
Polymorphism (computer science)
Internal medicine
Renin
CKD
medicine
Humans
SNP
Pharmacology (medical)
Molecular Biology
ADPKD
Aged
Biochemistry
medical
business.industry
Research
Biochemistry (medical)
Haplotype
Cell Biology
General Medicine
Middle Aged
Polycystic Kidney
Autosomal Dominant
medicine.disease
female genital diseases and pregnancy complications
030104 developmental biology
Endocrinology
030220 oncology & carcinogenesis
Chronic Disease
Female
business
Kidney disease
Zdroj: Journal of Biomedical Science
ISSN: 1423-0127
DOI: 10.1186/s12929-015-0217-0
Popis: Background Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder and is a common genetic cause of chronic renal failure in children and adults. The enzyme renin plays a key role in the RAAS cascade and an important role in the development of hypertension and progression of renal disease in ADPKD. The present study is aimed to investigate the potential modifier effect of REN gene polymorphisms on the progression of chronic kidney disease (CKD) in ADPKD. Methods We analyzed 102 ADPKD patients and 106 healthy controls from the same geographic area. FRET-based KASPar single-nucleotide polymorphism (SNP) genotyping assays for REN gene tag-SNPs (rs2887284, rs2368564, rs1464816, rs7521667, rs10900555, rs6693954, rs6676670 and rs11571078) were performed. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Haplotype frequencies and LD measures were estimated by using the software Haploview. Mantel-Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Results Of the eight tag-SNPs genotyped, the rs10900555 polymorphism deviated from the Hardy-Weinberg equilibrium in controls. The presence of ADPKD in general was not significantly associated with the REN tag-SNPs included in this study. Linkage disequilibrium analysis yielded three haplotype blocks and the haplotypes of the respective blocks are not statistically different between ADPKD and controls. In multivariate analysis, the rs1464816 TG genotype showed a significant association with the advancement of CKD in ADPKD (OR = 4.80; 95 % CI = 1.30–17.82; p = 0.019). Conclusions The present study provides evidence that the rs1464816 polymorphism in REN is associated with CKD progression in ADPKD. Electronic supplementary material The online version of this article (doi:10.1186/s12929-015-0217-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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