The incidence of type 2 diabetes is rising rapidly because of
The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. normal subjects were determined by linear regression analysis while controlling for age, gender and BMI. Association was tested using co-dominant, dominant and recessive models. Statistical analyses were performed using SAS software (SAS institute, Cary, NC, USA). Results Genome-wide linkage analysis in the 52705-93-8 whole study group Whole-genome linkage analysis using ASPs with 400 microsatellite markers was performed on 269 Korean ASPs (171 families) with type 2 diabetes. The observed value, with an NPL score corresponding to marker D4S3015 of 2.81 (LOD 2.27, and with type 2 diabetes-related phenotypes in normal control subjects. Results for the multiple regression analysis of association between and and BMI, waistChip ratio (WHR), and fasting insulin level are shown in Table 2. The SNPs were associated with BMI and WHR, and the SNPs were associated with fasting insulin level in 382 SNUH and 932 KHGS subjects. In the combined 1314 normal subjects (SNUH+KHGS), the rs13152426 and rs13144140 SNPs in were significantly associated with BMI (were significantly associated (or SNPs (data not shown). Table 2 Association results for candidate 52705-93-8 genes and type 2 diabetes-related phenotypes in normal subjects Discussion We statement here the first genome-wide search for chromosome loci associated with type 2 diabetes susceptibility in Korean subjects. Our results reveal evidence of linkage at the 4q34-35 locus in subjects with BMI?23?kg?m?2. The study is usually comprehensive because we performed 52705-93-8 genome-wide linkage analysis, fine mapping and association analysis with quantitative characteristics. Another strength of our study is that the ethnicity of the Korean populace is relatively homogeneous, resulting in a higher probability of identifying diabetes-linked loci. There have been more than 50 type 2 diabetes linkage analysis studies conducted in various populations, but few loci with strong evidence for linkage have been replicated.11 The 4q34-35 region showed a replicated linkage transmission that was reported in several populations. Significant evidence for linkage has been obtained for marker D4S1501 on 4q34 in Ashkenazi Jewish individuals,21 and modest evidence for linkage between type 2 diabetes and chromosome 4q34Cq35 was detected in Finnish families.22 In addition, the 4q34 region contains susceptibility loci in French whites.23 In the French study, the loci were detected when subjects were subdivided according to a BMI of 27?kg?m?2, which is similar to our approach. We used a BMI of 23?kg?m?2 as a cutoff value for being overweight. A WHO expert consultant considered whether a population-specific cutoff point for BMI was necessary, and concluded that a substantial proportion of the Asian population is at high risk for type 2 diabetes and that many Asians have BMIs lower than the existing WHO cutoff point for being overweight (?25?kg?m?2) compared with Caucasians (in general) or European populations.24 Another WHO report indicated that Asian adults with a BMI>23.0 should be considered overweight.25 We found evidence of linkage for type 2 diabetes from subgroups with BMI?23?kg?m?2. These results indicate an interaction between susceptibility loci and obesity. Moreover, subgrouping by BMI may have increased our chance of discovering risk loci. Conversely, subgrouping could lead to false-positive results. Because we confirmed our results 52705-93-8 in two replication sets and performed a quantitative trait analysis, however, the possibility of false positives seems low. acts as a stress-response gene 52705-93-8 during hippocampal formation. The relationship between variant, we analyzed the effect of the rs13144140 SNP (intron1, “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_201591″,”term_id”:”387598074″NM_201591) using an approach. The FASTSNP program allows users to efficiently identify and prioritize high-risk SNPs according to their phenotypic risks and putative functional effects.27 The analysis of rs13144140 with FASTSNP revealed that it is predicted to be a functional change in the protein by causing a change in a transcription factor binding sites. Using TRANSFAC,28 we found that rs13144140 correlated with binding of Rabbit polyclonal to ZNF490 HNF-1, a transcription factor that controls multiple genes implicated in pancreatic -cell function.29.