Type 2 Diabetes-related Gene Mapping

Aims: To search the type 2 diabetes susceptibility genes in Chinese population. Methods: A genome-wide scan was performed using both parametric and non-parametric linkage analyses. 102 families (478 family members) from Chinese Hans residing in the East and South-East China, including 282 diabetic patients, among them 142 independent affected sibpairs were available for genotyping. 247 fluorescence labeled microsatellite markers, with an average resolution of 15cM, were amplified. Genehunter and Mlink of Linkage package were used for the non-parametric and parametric linkage analyses. Results: Two loci on chromosome 9 D9S171 and D9S175 showed suggestive evidence for linkage, with Zall-score of 3.29 and 2.94 respectively, and p-value of 1.19×10-4 and 4.73×10-4. The corresponding Lod-score of these two loci were 4.61 and 4.29 respectively with the p-value of 2.44×10-5 and 5.14×10-5, under additive model. A locus on the long arm of chromosome 20 D20S196 showed a rise of Zall-score (from 1.52 to 2.92) and a corresponding decrease of p-value from 0.04 to 6.53×10-4 when families with lower BMI were analyzed alone. Other loci with weaker evidence for linkage were also observed. Conclusions: Our results suggest that chromosome 9 may contain genes involved in the susceptibility to type 2 diabetes in East and Southeast Chinese Han population, while chromosome 20 may hide genes that were linked to type 2 diabetes in families with lower BMI. Other regions may also hide susceptibility genes with minor effect, but further investigation is required to confirm the results. Aims: To find out SNPs of candidate genes near D9S175 in Chinese population and study their relationship with type 2 diabetes. Methods: Bidirectional sequencing was used to detect SNPs in the 5'regulatory regions, exons and partial introns close to exons of some candidate genes near D9S175. A preliminary estimation of the distribution of alleles in diabetic population and normal control population was performed using the the comparison of the ratio of pic-height of DNA pool of diabetic patients and of normal controls. Results: Four genes near D9S175 were screened for SNPs, they were RORB, FLJ20808, FLJ20087 and FRDA. 9 SNPs were discovered, among them 2 in 5'regulatory region, 1 in 5'UTR, 2 in exons and 4 in introns close to exons. The distribution of alleles was significantly different between the DNA pool of diabetic patients and that of normal control subjects only in RORBI9-59, the SNP in the 9th intron of RORB gene. Conclusion: SNP related to type 2 diabetes may exist in RORB gene, but the conclusion need to be confirmed with genotyping and association study in large samples.