Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls.

No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis.

Association studies have implicated common variants in the 12q14.1 region containing CYP27B1 in multiple sclerosis (MS). Rare CYP27B1 mutations cause autosomal recessive vitamin D-dependent rickets type 1, and it has recently been reported that heterozygous CYP27B1 mutations are associated with increased MS susceptibility and lower active vitamin D levels.

Rare MEFV variants are not associated with risk to develop multiple sclerosis and severity of disease.

Background: Recent studies suggest an association between rare variants in Mediterranean fever (MEFV), the gene underlying the auto-inflammatory disorder Familial Mediterranean Fever (FMF), the risk to develop multiple sclerosis (MS) and severity of MS.

Objective: The objective of this study is to investigate these findings in a Belgian MS population and to test for association with additional clinical parameters such as treatment response.

Methods: MEFV was sequenced in a cohort of MS patients (N=94) suffering from auto-inflammatory symptoms, systemic side-effects upon interferon-beta (IFN-β) treatment, or patients in whom glatiramer acetate was started as first choice due to severe fatigue.

TNFRSF1A coding variants in multiple sclerosis.

Patients with the autoinflammatory disease Tumour Necrosis Factor receptor-associated periodic syndrome (TRAPS) who suffer from demyelinating disease have been described, and one of the milder TRAPS mutations (R92Q in the TNFRSF1A gene) has been suggested as a risk factor for multiple sclerosis (MS). In a study population of 967 MS patients and 1022 controls, we replicate association [P=5×10⁻⁴, 3% in patients versus 1% in controls, OR=2.26 (95% CI 1.

Blood vessel density in de novo formed adipose tissue is decreased upon overexpression of TIMP-1.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in the development of obesity by contributing to adipogenesis, angiogenesis, and extracellular matrix degradation. We have evaluated a potential functional role of TIMP-1, which inhibits most MMPs, in in vivo adipogenesis. Therefore, human (h) TIMP-1 was overexpressed by injection in the tail vein of NUDE mice of an adenoviral vector 3 days before injection of 3T3-F442A preadipocytes in the back.

Effect of tissue inhibitor of matrix metalloproteinases-1 on in vitro and in vivo adipocyte differentiation.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in development of obesity by contributing to adipogenesis, angiogenesis and extracellular matrix degradation. We have evaluated a potential functional role of TIMP-1, which inhibits most MMPs, in early stages of in vitro and in vivo adipogenesis. Overexpression of human TIMP-1 (hTIMP-1) in 3T3-F442A preadipocytes resulted in a somewhat slower differentiation into mature adipocytes, without affecting the total extent of differentiation.