Variants in the RARRES2 gene are associated with serum chemerin and increase the risk of diabetic kidney disease in type 2 diabetes.

Genetic susceptibility plays an important role in the pathogenesis of diabetic kidney disease (DKD). Recent studies have suggested that chemerin (encoded by the RARRES2 gene) is a risk factor for the development of DKD. We investigate the relationship between RARRES2 single nucleotide polymorphisms (SNPs) and DKD and their correlation with serum chemerin levels in Chinese individuals with type 2 diabetes (T2D). A total of 256 individuals with T2D were enrolled in this case-control study and classified into normo-, micro- and macroalbuminuria groups according to their urinary albumin/creatinine ratio (UACR). All exons of the RARRES2 gene were sequenced by polymerase chain reaction-direct sequencing, and 7 SNPs were genotyped. We found that the minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with macroalbuminuria. Carriers of the minor allele of rs1047575 and rs1047586 also had higher urinary albumin (U-Alb) and UACR levels under both homo- and heterozygotic conditions than carriers of the major allele under the homozygotic condition. The minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with increased serum chemerin levels under the homozygotic condition. These SNPs in the RARRES2 gene probably affect chemerin expression and likely confer susceptibility to albuminuria in individuals with T2D.