Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish Population Based Case-Control Study

<div><p>Introduction</p><p>The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort.</p><p>Methods</p><p>Periodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry (DHR), where dental diagnostic- and treatment codes on the adult Swedish population have been registered. Dental records from 100 cases and controls were reviewed to validate the periodontal diagnostic codes in DHR.</p><p>Results</p><p>The reviewed dental records confirmed 90% of the periodontitis diagnoses in DHR among RA cases, and 88% among controls. We found the positive predictive value of periodontitis diagnoses in the DHR to be 89% (95% CI 78 to 95%) with a sensitivity of 77% (95% CI: 65 to 86%). In total, 86% of EIRA participants were identified in DHR. The risk for periodontitis increased by age and current smoking status in both cases as well as controls. No significant differences in prevalence of periodontal disease in terms of gingivitis, periodontitis, peri-implantitis or increased risk for periodontitis or peri-implantitis were observed between RA cases and controls. In addition, there was no difference on the basis of seropositivity, ACPA or rheumatoid factor (RF), among patients with RA.</p><p>Conclusions</p><p>Our data verify that smoking and ageing are risk factors for periodontitis, both in RA and controls. We found no evidence of an increased prevalence of periodontitis in patients with established RA compared to healthy controls, and no differences based on ACPA or RF status among RA subjects.</p></div

Prevalence of periodontitis in relation to age.

<p>Prevalence (%) and numbers of exposed participants with periodontitis in different age groups identified in DHR demonstrating, (<b>A)</b> RA cases versus controls, (<b>B)</b> ACPA-positive versus ACPA-negative RA patients, (<b>C)</b> RA-women versus RA-men, (<b>D)</b> control-women versus control-men. Statistical differences were observed with increased age for both RA cases and controls. The differences between the groups were analysed by chi-square test or Fisher´s exact test. p-value < 0.05 was considered statistically significant.</p

EIRA RA cases and controls with periodontal diagnostic codes identified in DHR, in relation to ACPA and RF status.

<p>EIRA RA cases and controls with periodontal diagnostic codes identified in DHR, in relation to ACPA and RF status.</p

Association between periodontal codes and smoking habits among RA cases and controls, as compared to never smokers, stratified by gender.

<p>Association between periodontal codes and smoking habits among RA cases and controls, as compared to never smokers, stratified by gender.</p

Characteristics of the total EIRA study population identified in DHR.

<p>Characteristics of the total EIRA study population identified in DHR.</p

Study design.

<p>Schematic overview of the study, including linkage of EIRA (Epidemiological Investigation of Rheumatoid Arthritis) with DHR (Dental Health Registry) and the validation of the diagnostic codes from DHR using dental records.</p

EIRA RA cases and controls with periodontal treatment codes, in relation to ACPA status.

<p>EIRA RA cases and controls with periodontal treatment codes, in relation to ACPA status.</p