Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.

Background: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms.

Methods And Results: In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.

A large candidate-gene association study suggests genetic variants at IRF5 and PRDM1 to be associated with aggressive periodontitis.

Aim: Epidemiological and clinical studies indicated a relationship of periodontitis with rheumatoid arthritis (RA). We aimed to identify shared genetic susceptibility loci of RA and periodontitis.

Materials And Methods: Forty-seven risk genes of genome-wide significance of RA and SLE were genotyped in a German case-control sample of aggressive periodontitis (AgP), using Immunochip genotyping arrays (Illumina, 600 cases, 1440 controls) and Affymetrix 500 K Genotyping Arrays (280 cases and 983 controls).

SLC23A1 polymorphism rs6596473 in the vitamin C transporter SVCT1 is associated with aggressive periodontitis.

Aim: Identification of variants within genes SLC23A1 and SLC23A2 coding for vitamin C transporter proteins associated with aggressive (AgP) and chronic periodontitis (CP).

Material And Methods: Employment of three independent case-control samples of AgP (I. 283 cases, 979 controls; II.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

Aim: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP).

Material And Methods: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip.

Common genetic risk variants of TLR2 are not associated with periodontitis in large European case-control populations.

Aim: Involvement of TLR2 in the pathophysiology of periodontitis has widely been discussed, but hitherto, no validated genetic associations were reported. Previous association studies lacked sufficient statistical power and adequate haplotype information to draw unambiguous conclusions. The aim of this study was to comprehensively investigate TLR2 linkage disequilibrium (LD) regions for their potential associations with periodontitis in two large analysis populations of aggressive (AgP) and chronic periodontitis (CP) of North West European descent.

CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection.

Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313).