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, LC Sciences’ 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.

Tag SNPs of let-7a-2 regulatory region were selected by the international HapMap project

LC Sciences

(A): The distribution of SNPs in let-7a-2 gene regulatory region(< 2.8 kb) in four populations which International HapMap project sampled. Population descriptors:YRI: Yoruba in Ibadan, Nigeria; JPT: Japanese in Tokyo, Japan; CHB: Han Chinese in Beijing, China; CEU: CEPH (Utah residents with ancestry from northern and western Europe); (B): Hapview 4.1 screened out six tag SNPs of let-7a-2 gene regulatory region. Haploview linkage disequilibrium (LD) plot showing the haplotype blocks.

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Reference

Zhou J, Peng R, Li T, Luo X, Peng H, Zha H, Yin P, Wen L, Zhang Z. (2013) A potentially functional polymorphism in the regulatory region of let-7a-2 is associated with an increased risk for diabetic nephropathy. Gene 527(2):456-61. [abstract]