Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity.

We examined the association between plasma 25-hydroxyvitamin D [25(OH)D] concentration and islet autoimmunity (IA) and whether vitamin D gene polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe. We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A) on two or more visits. We conducted a risk set sampled nested case-control study of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D concentration was measured on all samples prior to, and including, the first IA positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry, higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood 25(OH)D was associated with a decreasing IA risk based upon number of minor alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92). Vitamin D and VDR may have a combined role in IA development in children at increased genetic risk for type 1 diabetes.

Twelve serum proteins progressively increase with disease stage in squamous cell cervical cancer patients.

OBJECTIVE: This study aimed to reliably identify serum protein profile alterations that may be useful for elucidation of the disease mechanism and/or finding new targets for treatment and intervention. MATERIALS AND METHODS: A total of 1057 women at 4 different squamous cell cervical cancer stages (noninvasive, invasive International Federation of Gynecology and Obstetrics stages I, II, and III) were included in this cross-sectional study. Forty-seven serum proteins were profiled using multiplex Luminex immunoassays. RESULTS: Serum concentration of serum amyloid A (SAA), C-reactive protein (CRP), soluble tumor necrosis factor receptor I and II (sTNFRI and sTNFRII), soluble interleukin 2 receptor α (sIL2Rα), CXCL1, CXCL9, hepatocyte growth factor, squamous cell carcinoma antigen (SCCA), insulin-like growth factor binding protein 2, CA125, and carcinoembryonic antigen (CEA) were elevated significantly as disease progressed in cervical cancer patients. Serum levels are significantly different at early stage (I) for SAA, CRP, sIL2Rα, sTNFRII, SCCA, and CEA (P values ranged from 0.02 for CEA to 0.0001 for CRP and SCCA) and at late stages (II and III) for all 12 proteins (P values ranged from 8.78E-5 for CA125 to 3.49E-47 for SAA), as compared to the noninvasive stage. The areas under the curves of these proteins for disease state separation also improved with the advancement of the disease. The correlations between serum concentrations of these proteins also show different patterns at different clinical stages. These proteins are involved in multiple mechanisms including inflammation and immunity, angiogenesis, growth promotion, and metastasis. CONCLUSIONS: A number of serum proteins are significantly different between patients at different stages of cervical cancer.