BACKGROUND: Polymorphisms in the UNC13B gene are associated with diabetic kidney disease (DKD) in the European population. Asian populations are more likely to suffer from complications of type 2 diabetes mellitus (T2DM), including diabetic kidney disease (DKD). This case-control study aimed to investigate the association between UNC13B gene polymorphisms and DKD in a Chinese Han population.

MATERIAL AND METHODS: Five single nucleotide polymorphism (SNP) loci (rs13293564, rs17360668, rs10114937, rs661712, and rs2281999) were genotyped in the UNC13B gene in 600 Chinese Han subjects. The study population included patients with T2DM with DKD (N=292) and control patients with T2DM without DKD (N=308). SNP genotyping was performed using a Sequenom MassARRAY system using chip-based matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

RESULTS: There were no significant differences in the distribution of allele or genotype frequencies in the five UNC13B SNP markers (rs13293564, rs17360668, rs10114937, rs661712, and rs2281999) between the DKD group and control group of patients with T2DM. Haplotype analysis identified eight haplotypes for the combined effect of the five SNP markers in the UNC13B gene. The haplotype GGCCG was significantly associated with an increased risk of DKD.

CONCLUSIONS: This was the first study to demonstrate an association between UNC13B gene polymorphisms and the susceptibility to DKD in a Chinese Han population with T2DM. The haplotype GGCCG was significantly associated with an increased risk of DKD. The findings highlight the joint effect of SNP markers in the pathogenesis of DKD.

Keywords: Genetic Association Studies, Structural Homology, Protein, Alleles, Asians, Case-Control Studies, Diabetes Mellitus, Type 2, ethnicity, Gene Frequency, Genetic Predisposition to Disease, Genotype, Haplotypes, Nerve Tissue Proteins, Polymorphism, Single Nucleotide