Objective: To search for the susceptibility variant (s) of type 2 diabetes in the susceptible regions on chr.1 (1p36.23-36.33, 1q24.3-25.1, and 1q42.12-42.13) by genotyping SNP markers in case-control DNA samples and identifying the haplotype associated with type 2 diabetes.
Methods: Totally 124 SNPs in 33 candidate genes in the mapped regions were chosen from public SNP data or identified by sequencing the samples that were used to search for SNP locus. Sequencing method was used to genotype the loci for 236 sporadic type 2 diabetes patients and 152 normal subjects in Northern Han Chinese population. The haplotypes with significant difference were further analyzed.
Results: Of 124 SNPs successfully typed, 4 SNPs that showed association with diabetes status were found: rs203849 (P=0.005, OR=1.60) and rs203826 (P=0.016, OR=1.60) located in sAC gene, rs7535528 (P=0.028, OR=1.45) located in PANK4, rs884363 (P=0.043, OR=1.37) located in CASP9 gene. In addition, the frequencies of two combination types from these 4 SNP genotypes were significantly different between case and control groups (P < 0.001). Furthermore, four haplotypes associated with diabetes were found in haplotype analysis of sAC gene.
Conclusion: sAC, PANK4, and CA SP9 may be associated with type 2 diabetes in Han population in north China, and it seems that the synergetic effect of these genes is responsible for the development of type 2 diabetes.