Clinical demographics of study population.

<p>^a<i>P</i> value < 0.05 compared with non-MetS control subject in multiple comparison using Dunnett’s test.</p><p>^b<i>P</i> value < 0.05 compared with non-MetS T2D patients in multiple comparison using Dunnett’s test.</p><p>Abbreviations: BMI, body mass index; HDL-C, high density lipoprotein-cholesterol; HOMA-B, the homeostasis model assessment for β-cell function; HOMA-IR, the homeostasis model assessment for insulin resistance; ISIm, Matsuda index; MetS, metabolic syndrome; OGTT, oral glucose tolerance test; T2D, type 2 diabetes. Data are shown as median (interquartile range) or %. All non-Gaussian distributed quantitative traits were natural logarithmically transformed to normalize distributions. <i>P</i> values were calculated to assess the intergroup differences using χ² test or one-way ANOVA.</p

The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes

<div><p>Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near <i>BCL11A</i>, rs10830963 in <i>MTNR1B</i>, and rs2237895 in <i>KCNQ1</i> were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00), <i>P</i> = 4.42 × 10⁻²; rs10830963: 0.92 (0.85, 1.00), <i>P</i> = 4.07 × 10⁻²; rs2237895: 0.89 (0.82, 0.98), <i>P</i> = 1.29 × 10⁻²). The T2D risk alleles of rs972283 near <i>KLF14</i> contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22), <i>P</i> = 4.48 × 10⁻²), while the T2D risk allele of rs7903146 in <i>TCF7L2</i> was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90), <i>P</i> = 2.56 × 10⁻³). The T2D risk alleles of rs972283 near <i>KLF14</i> and rs11634397 near <i>ZFAND6</i> were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), <i>P</i> = 1.46 × 10⁻²; rs11634397: 1.14 (1.00, 1.29), <i>P</i> = 4.66 × 10⁻²), while the T2D risk alleles of rs780094 in <i>GCKR</i> and rs7903146 in <i>TCF7L2</i> were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), <i>P</i> = 1.35 × 10⁻⁴; rs7903146: 0.82 (0.69, 0.98), <i>P</i> = 3.18 × 10⁻²). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity (<i>P</i>_trend = 1.29 × 10⁻²) and lower waist circumference (<i>P</i> = 2.20 × 10⁻³). Genetic variants of <i>WFS1</i>, <i>CDKAL1</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>HHEX</i>, <i>KCNQ1</i>, <i>TSPAN8/LGR5</i>, <i>FTO</i>, and <i>TCF2</i> were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (<i>P</i> < 0.05). In addition, genetic variants of <i>BCL11A</i>, <i>GCKR</i>, <i>ADAMTS9</i>, <i>CDKAL1</i>, <i>KLF14</i>, <i>CDKN2BAS</i>, <i>TCF7L2</i>, <i>CDC123/CAMK1D</i>, <i>HHEX</i>, <i>MTNR1B</i>, and <i>KCNQ1</i> contributed to the risk for T2D without MetS (<i>P</i> < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation.</p></div

Additional file 1: of Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Search terms used for database searches. (DOCX 18 kb

Additional file 4: of Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Clinical findings for cases with monoallelic mutation. (DOCX 56 kb

Additional file 2: of Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Included and excluded articles. (DOCX 161 kb

Clinical characteristics of the study population.

<p>Abbreviations: BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; HOMA-B, the homeostasis model assessment for β-cell function; HOMA-IR, the homeostasis model assessment for insulin resistance; LDL-C, low-density lipoprotein cholesterol; OGTT, oral glucose tolerance test; ISIm, Matsuda index; WC, waist circumference. Data are shown as median (interquartile range) or %.</p><p>Clinical characteristics of the study population.</p

Genetic Variants Associated with Lipid Profiles in Chinese Patients with Type 2 Diabetes

<div><p>Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (<i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, <i>DOCK7</i>, <i>HNF1A</i>, and <i>HNF4A</i>) were genotyped. After adjusting for multiple covariates, SNPs in <i>ABCA1</i>, <i>GCKR</i>, <i>BAZ1B</i>, <i>TOMM40</i>, and <i>HNF1A</i> were identified as significantly associated with triglyceride levels in T2D patients (<i>P</i> < 0.05). The associations between the SNPs in <i>ABCA1</i> (rs3890182), <i>GCKR</i> (rs780094), and <i>BAZ1B</i> (rs2240466) remained significant even after correction for multiple testing (<i>P</i> = 8.85×10⁻³, 7.88×10⁻⁷, and 2.03×10⁻⁶, respectively). <i>BAZ1B</i> (rs2240466) also was associated with the total cholesterol level (<i>P</i> = 4.75×10⁻²). In addition, SNP rs157580 in <i>TOMM40</i> was associated with the low-density lipoprotein cholesterol level (<i>P</i> = 6.94×10⁻³). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes.</p></div

Additional file 3: of Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review

Clinical findings for cases with biallelic mutations. (DOCX 96 kb

Table_2_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.xlsx

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p

Image_2_A Novel Stool Methylation Test for the Non-Invasive Screening of Gastric and Colorectal Cancer.tif

BackgroundBecause of poor compliance or low sensitivity, existing diagnostic approaches are unable to provide an efficient diagnosis of patients with gastric and colorectal cancer. Here, we developed the ColoCaller test, which simultaneously detects the methylation status of the SDC2, TFPI2, WIF1, and NDRG4 genes in stool DNA, to optimize the screening of gastric and colorectal cancer in high-risk populations.MethodsA total of 217 stool samples from patients with gastrointestinal cancer and from patients with negative endoscopy were prospectively collected, complete with preoperative and postoperative clinical data from patients. The methylation of these samples was detected using ColoCaller, which was designed by selecting CpGs with a two-step screening strategy, and was interpreted using a prediction model built using libSVM to evaluate its clinical value for gastric and colorectal cancer screening.ResultsCompared to pathological diagnosis, the sensitivity and specificity of the ColoCaller test in 217 stool DNA samples were 95.56% and 91.86%, respectively, for colorectal cancer, and 67.5% and 97.81%, respectively, for gastric cancer. The detection limit was as low as 1% in 8 ng of DNA.ConclusionIn this study, we developed and established a new test, ColoCaller, which can be used as a screening tool or as an auxiliary diagnostic approach in high-risk populations with gastric and colorectal cancer to promote timely diagnosis and treatment.</p