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- Gu, HF, et al.
(författare)
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Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 53:8, s. 2137-2142
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-degrading enzyme (IDE) plays a principal role in the proteolysis of several peptides in addition to insulin and is encoded by IDE, which resides in a region of chromosome 10q that is linked to type 2 diabetes. Two recent studies presented genetic association data on IDE and type 2 diabetes (one positive and the other negative), but neither explored the fundamental question of whether polymorphism in IDE has a measurable influence on insulin levels in human populations. To address this possibility, 14 single nucleotide polymorphisms (SNPs) from a linkage disequilibrium block encompassing IDE have been genotyped in a sample of 321 impaired glucose tolerant and 403 nondiabetic control subjects. Analyses based on haplotypic genotypes (diplotypes), constructed with SNPs that differentiate common extant haplotypes extending across IDE, provided compelling evidence of association with fasting insulin levels (P = 0.0009), 2-h insulin levels (P = 0.0027), homeostasis model assessment of insulin resistance (P = 0.0001), and BMI (P = 0.0067), with effects exclusively evident in men. The strongest evidence for an effect of a single marker was obtained for rs2251101 (located near the 3′ untranslated region of IDE) on 2-h insulin levels (P = 0.000023). Diplotype analyses, however, suggest the presence of multiple interacting trait-modifying sequences in the region. Results indicate that polymorphism in/near IDE contributes to a large proportion of variance in plasma insulin levels and correlated traits, but questions of sex specificity and allelic heterogeneity will need to be taken into consideration as the molecular basis of the observed phenotypic effects unfolds.
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| 3. |
- Gu, HF, et al.
(författare)
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Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 5353 Suppl 1, s. S31-S35
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin (APM1) is an adipocyte-derived peptide. The APM1 gene is located on chromosome 3q27 and linked to type 2 diabetes. In patients with type 2 diabetes, the adiponectin level in plasma is decreased in comparison to healthy subjects. To identify genetic defects of the APM1 gene that contribute to the development of type 2 diabetes, we genotyped 13 single nucleotide polymorphisms (SNPs) in 106 patients with type 2 diabetes, 325 patients with impaired glucose tolerance (IGT), and 497 nondiabetic control subjects in Swedish Caucasians by using dynamic allele-specific hybridization (DASH). We found that SNPs −11426(A/G) and −11377(G/C) in the proximal promoter region had significant differences of allele frequencies between type 2 diabetic patients and nondiabetic control subjects (P = 0.02 and P = 0.04, respectively). SNP-11426(A/G) was significantly associated with fasting plasma glucose in type 2 diabetic patients (P = 0.02) and in IGT subjects (P = 0.04), while the patients carrying CC and CG genotypes for SNP-11377(G/C) had a higher BMI than the patients with the GG genotype (P = 0.03). Haplotype analysis of 13 SNPs in the APM1 gene showed that estimates of haplotype frequencies in Swedish Caucasians are similar to those estimated in French Caucasians. However, no significant association of haplotypes with type 2 diabetes and IGT was detected in our study. The present study provides additional evidence that SNPs in the proximal promoter region of the APM1 gene contribute to the development of type 2 diabetes.
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