Regional cerebral blood flow in fibromyalgia Single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami

Copyright © 2009 American College of Rheumatology The definitive version may be found at www.wiley.comTo determine whether regional cerebral blood flow (rCBF) is abnormal in any cerebral structure of women with fibromyalgia (FM), following a report that rCBF is reduced in the thalami and heads of caudate nuclei in FM. Methods Seventeen women with FM and 22 healthy women had a resting single-photon–emission computed tomography (SPECT) brain scan to assess rCBF and a T1-weighted magnetic resonance imaging (MRI) scan to enable precise anatomic localization. Additionally, all participants underwent 2 manual tender point examinations and completed a set of questionnaires evaluating clinical features. SPECT scans were analyzed for differences in rCBF between groups using statistical parametric mapping (SPM) and regions of interest (ROIs) manually drawn on coregistered MRI. Results Compared with control subjects, the rCBF in FM patients was significantly reduced in the right thalamus (P = 0.006), but not in the left thalamus or head of either caudate nucleus. SPM analysis indicated a statistically significant reduction in rCBF in the inferior pontine tegmentum (corrected P = 0.006 at the cluster level and corrected P = 0.023 for voxel of maximal significance), with consistent findings from ROI analysis (P = 0.003). SPM also detected a reduction in rCBF on the perimeter of the right lentiform nucleus. No correlations were found with clinical features or indices of pain threshold. Conclusion Our finding of a reduction in thalamic rCBF is consistent with findings of functional brain imaging studies of other chronic clinical pain syndromes, while our finding of reduced pontine tegmental rCBF is new. The pathophysiologic significance of these changes in FM remains to be elucidated.Richard Kwiatek, Leighton Barnden, Raymond Tedman, Richard Jarrett, Jenni Chew, Christopher Rowe, Kevin Pil

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease (AITD), multiple sclerosis ( MS) and breast cancer ( BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' disease