title: A potentially functional polymorphism in the regulatory region of let-7a-2 is associated with an increased risk for diabetic nephropathy.
abstract: Diabetic nephropathy (DN) is a major diabetic complication. However, the initiating molecular events triggering DN are unknown. MicroRNAs (miRNAs) have recently been identified as regulators that modulate the target gene expression and are involved in DN. However, the evidence of the mechanism is still insufficient in human samples. In this study, microRNA microarray assay was used to study gene differential expression profiles in DN and diabetes mellitus (DM) patients. One of the specific differentially expressed microRNAs, let-7a, was down-expressed in DN. Additionally, the expression of let-7a was also decreased in DN by real-time RT PCR in the patients' samples. Moreover, single nucleotide polymorphism (SNP) analysis was used to evaluate the relationship between three SNPs in the regulatory region of let-7a-2 gene and the risk of DN in the Chinese Han population by means of PCR-restriction fragment length polymorphism (RFLP-PCR). Also, the genotype and allele frequencies of let-7a-2 polymorphism were tested in 274 individuals, including 108 DN, 104 DM patients and 62 health control individuals (CON). It was found that a variant rs1143770 and the distributions of CT/TT genotypes were significantly different in three groups, and the CT+TT genotypes frequencies were significantly higher in DN and DM groups than that in CON group. In conclusion, let-7a-2 might participate in the regulation of the occurrence of DN, and a potential variant rs1143770 was significantly associated with the increased risk for DN.
authors.affiliation: Department of Cell Biology and Medical Genetics, Chongqing Medical University, No.1, Medical College Road, Chongqing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.forename: Tianju
authors.initials: T
authors.lastname: Li
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Luo
authors.forename: Huimin
authors.initials: H
authors.lastname: Peng
authors.forename: He
authors.initials: H
authors.lastname: Zha
authors.forename: Pin
authors.initials: P
authors.lastname: Yin
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D003928:Diabetic Nephropathies / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D035683:MicroRNAs
keywords: CREB; DM; DN; Diabetic nephropathy; HbA1c; LD; MAF; MicroRNA; PCR-RFLP; PCR-restriction fragment length polymorphism; SNP; SNPs; UARE; cyclic adenosine monophosphate response element-binding protein; diabetes mellitus; diabetes mellitus with diabetic nephropathy; hemoglobin a1c; linkage disequilibrium; minor allele frequency; single nucleotide polymorphism; urinary albumin excretion rate