No associations between single nucleotide polymorphisms in corticoid receptor genes and heart rate and cortisol responses to a standardized social stress test in adolescents: the TRAILS study.

Previously, sequence variation in the glucocorticoid (GR) and mineralocorticoid (MR) receptor genes (NR3C1 and NR3C2, respectively) have been found to be associated with physiological stress responses to social stress tests in small samples of adult men and oral contraceptives (OC) using women. Associations between single nucleotide polymorphisms (SNPs) in the GR (23EK-rs6190, 9beta-rs6198, BclI-rs4142324) and the MR gene (I180V-rs5522 and -2G/C (rs2070951) with cortisol and heart rate responses to a performance-related social stress task (public speaking and mental arithmetic) were examined in a large sample (n = 553) of adolescents (15-17 years). To make comparisons with previous findings, associations were tested in boys (n = 277), free-cycling (FC) girls (n = 183) and OC users (n = 93).

Multiple common variants for celiac disease influencing immune gene expression.

We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection.

Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (TRacking Adolescents' Individual Lives Survey) Study.

Background: Overweight is a complex trait in which both environmental and genetic factors play a role.

Objective: We aimed to evaluate the influence of common genetic variants identified by genome-wide association studies on overweight and the metabolic profile in adolescence.

Design: In a population-based cohort of 663 girls and 612 boys aged 16 y, weight, height, skinfold thicknesses, percentage body fat, waist circumference, blood pressure, glucose, insulin, lipid profile, and DNA were obtained.

Runt-related transcription factor 3 is associated with ulcerative colitis and shows epistasis with solute carrier family 22, members 4 and 5.

Background: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are intestinal inflammatory disorders with a complex genetic background. Mice deficient for the runt-domain-transcription-factor3 (Runx3) develop spontaneous colitis. Human RUNX3 resides in an IBD-susceptibility locus.

Association of interleukin-1 receptor-associated kinase M (IRAK-M) and inflammatory bowel diseases.

Objective: Inflammatory bowel diseases (IBD) have a complex genetic background. The interleukin receptor associated kinase-M (IRAK-M) is a NF-kappaB-mediated, negative regulator of Toll-like receptor (TLR) signaling. A functional mutation in a negative regulator might induce impaired endotoxin tolerance and increased inflammatory responses.

Absence of association between the multidrug resistance (MDR1) gene and inflammatory bowel disease.

Objective: The multidrug resistance (MDR1) gene encodes for P-glycoprotein, a drug efflux pump. Mice deficient for the MDR1a gene spontaneously develop colitis. In humans, a polymorphism in exon 26 (C3435T) is associated with reduced expression levels and function of MDR1.

No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors.

CHEK2 is low-penetrance breast cancer susceptibility gene. The 1100delC mutation may interact with variants/mutations in other breast cancer susceptibility loci. We identified a risk haplotype in the HLA class III region in breast cancer patients [de Jong MM, Nolte IM, de Vries EGE, et al.

Association between Toll-like receptor 4 and inflammatory bowel disease.

Background: The human Toll-like receptor 4 (TLR4) participates in the innate response. Recently, the TLR4 variant Asp299Gly has been described to affect the response of this receptor to lipopolysaccharide. As such, there is a potentially important role of TLR4 in the pathogenesis of inflammatory bowel disease (IBD).

Methylenetetrahydrofolate reductase (MTHFR) and susceptibility for (pre)neoplastic cervical disease.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating the metabolism of folate and methionine. The potential influence of MTHFR activity on DNA methylation and on the availability of uridylates and thymidylates for DNA synthesis and repair presents MTHFR as a candidate for being a cancer-predisposing gene. In the present study, we have examined a large study population to determine whether the C677T polymorphism at the MTHFR locus affects susceptibility for cervical cancer or its precursor, cervical intraepithelial neoplasia (CIN).

The HLA class III subregion is responsible for an increased breast cancer risk.

BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region.