Additional file 1: Table S1. of Method for estimating high sdLDL-C by measuring triglyceride and apolipoprotein B levels

Alternative LDL window in healthy subjects. Table S2. Alternative LDL window in patients with type 2 diabetes. Table S3. Alternative LDL window in 528 patients with CAD including diabetes. (DOCX 29 kb

Suppressive effects of GIP on the progression of atherosclerotic lesions in diabetic <i>Apoe</i>^−/− mice.

<p>Thirty-five mice at 15 weeks of age were made diabetes by peritoneal injection of STZ (50 mg/kg/day) for 5 days and 14 mice were untreated. The 17-week-old diabetic <i>Apoe</i>^−/− mice were infused for 4 weeks with vehicle (control), GIP (25 nmol/kg/day), or GIP+[Pro³]GIP (both 25 nmol/kg/day) by osmotic mini-pumps. The aortic surface was stained with oil red O. Cross-sections of the aortic root were stained with oil red O or anti-MOMA-2 antibody. Hematoxylin was used for nuclear staining. The areas occupied by atherosclerotic lesions and by macrophage infiltration in the aortic wall were determined.</p

Expression of GIPR in pancreatic islets from <i>db/misty</i> and <i>db/db</i> mice.

<p>GIPR was stained with goat polyclonal anti-GIPR antibody. Hematoxylin was used for nuclear staining. Representative results are shown.</p

Expression of GIPR in exudate peritoneal macrophages from nondiabetic and diabetic <i>Apoe</i>^−/− mice.

<p>GIPR was stained with goat polyclonal anti-GIPR antibody followed by anti-goat Alexa Fluor 568. Phalloidin/DAPI staining shows F-actin cytoskeleton and nuclear morphology of mouse macrophages. These images were merged. Representative results are shown.</p

<i>In vitro</i> suppressive effects of GIP on foam cell formation in exudate peritoneal macrophages from nondiabetic and diabetic <i>Apoe</i>^−/− mice.

<p>Exudate peritoneal macrophages were obtained from 6 nondiabetic <i>Apoe</i>^−/− mice (A) and 6 STZ-induced diabetic <i>Apoe</i>^−/− mice (B) by intraperitoneal injection of thioglycolate, and were incubated with or without GIP (1 nM) for 24 hours followed by addition of oxLDL (10 µg/ml) for 18 hours. Foam cell formation was evaluated by oxLDL-induced CE accumulation in macrophages. Assays were performed in duplicate. 1 fold = 15.6±1.5 nmol/mg cell protein (A) and 13.8±1.0 nmol/mg cell protein (B).</p

Foam cell formation in exudate peritoneal mouse macrophages.

<p><b>A</b>, 12 <i>Apoe</i>^−/− mice at 15 weeks of age were made diabetes by peritoneal injection of STZ (50 mg/kg/day) for 5 days and 6 <i>Apoe</i>^−/− mice were untreated. The 17-week-old diabetic <i>Apoe</i>^−/− mice were infused for 4 weeks with vehicle, GIP (25 nmol/kg/day), or GIP+[Pro³]GIP (both 25 nmol/kg/day) by osmotic mini-pumps. <b>B</b>, 6 <i>db/misty</i> mice and 6 <i>db/db</i> mice at 8 weeks of age were started to be infused with saline and 6 <i>db/db</i> mice were ifused with GIP (25 nmol/kg/day). Four weeks after infusions, exudate peritoneal macrophages were obtained from these mice by intraperitoneal injection of thioglycolate, and incubated with oxLDL (10 µg/ml) for 18 hours. Foam cell formation was evaluated by oxLDL-induced CE accumulation in macrophages. Assays were performed in duplicate or single. 1 fold = 17.5±1.0 nmol/mg cell protein (A) and 14.7±1.2 nmol/mg cell protein (B).</p

General characteristics and plasma measurements.

a<p> = vs. Nondiabetic,</p>b<p> = vs. Diabetic,</p>c<p> = Diabetic GIP at <i>P</i><0.001–0.05.</p

Multiple SNPs in Intron 41 of Thyroglobulin Gene Are Associated with Autoimmune Thyroid Disease in the Japanese Population

<div><h3>Background</h3><p>The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the US identified a locus on chromosome 8q24 that showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between thyroglobulin (Tg) polymorphisms and AITD in Caucasians, suggesting that Tg is a susceptibility gene on 8q24.</p> <h3>Objectives</h3><p>The objective of the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs across an extended 260 kb region of the Tg.</p> <h3>Methods</h3><p>We studied 458 Japanese AITD patients (287 GD and 171 HT patients) and 221 matched Japanese control subjects in association studies. Case-control association studies were performed using 25 Tg single nucleotide polymorphisms (SNPs) chosen from a database of the Single Nucleotide Polymorphism Database (dbSNP). Haplotype analysis was undertaken using the computer program SNPAlyze version 7.0.</p> <h3>Principal Findings and Conclusions</h3><p>In total, 5 SNPs revealed association with GD (P<0.05), with the strongest SNP associations at rs2256366 (P = 0.002) and rs2687836 (P = 0.0077), both located in intron 41 of the Tg gene. Because of the strong LD between these two strongest associated variants, we performed the haplotype analysis, and identified a major protective haplotype for GD (P = 0.001).These results suggested that the Tg gene is involved in susceptibility for GD and AITD in the Japanese.</p> </div

Case–control association results for the two most highly GD associated SNPs.

<p>Values given are the number of subjects, with the percentage in parentheses.</p>a<p>P-value based on χ² distribution.</p

Tg haplotype structure and frequencies^a.

a<p>The program, SNPAlyze ver. 7.0 Standard, was used to estimate common (frequencies >0.01) haplotypes for the two SNPs genotyped.</p>b<p>Each haplotype was compared with the other haplotypes combined.</p