A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis

Abstract

Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci

“…Likewise, ORM1 may play a significant role in the regulation of fibrinolysis. We consider this as relevant, because variants with putative ciseffects on the expression of PLG were previously found to be associated with both AgP and CP [21,22] and an Fig. 3 Regional association plots of the loci with P < 10 −6 for the lead variants identified after removing the smallest sample of AgP-NL.…”

“…The third variant, SNP rs2064712, was associated with P = 5.29 × 10 −7 (OR = 1.24, 95% CI = [1.14-1.35]) and located on chromosome 6 between unprocessed pseudogene AL109933.3 and lincRNA AL391361.2 and 42 kb downstream of PLG (Plasminogen). The PLG locus had earlier been identified by us as a susceptibility locus for PD in the same analyses samples in a candidate-gene association study, where it was tagged by the GWAS SNP rs1247559 (r 2 < 0.2 with rs2064712) [22]. Rs1247559 had a P-value of 2.25 × 10 −5 in the meta-analysis of AgP-Ger, CP-EA-mod and CP-EA-sev and was not pursued further in the current study.…”

“…In this study, two common variants at SIGLEC5 and DEFA1A3 reached genome-wide significance in the combined sample [20]. Currently, these variants are the only shared risk variants of CP and AgP identified by GWAS, together with two haplotype blocks at PLG (plasminogen) and at the gene cluster PF4 (platelet factor 4)/PPBP (pro-platelet basic protein)/CXCL5 (C-X-C motif chemokine ligand 5), which were identified by different approaches [21][22][23]. In the current study, we aimed to identify additional common susceptibility variants for AgP and CP by conducting a meta-analysis with our North-West European GWAS of AgP and a European-American GWAS of CP.…”

Aggregatibacter, a Low Abundance Pathobiont That Influences Biogeography, Microbial Dysbiosis, and Host Defense Capabilities in Periodontitis: The History of a Bug, and Localization of Disease

“…While several genes have been implicated as unique to those with LAgP (using the restrictive definition outlined above), data are limited because of: (1) the rarity of the disease; and (2) the use of broad inaccurate definitions of the disease. If the disease is limited to adolescents of African descent showing the distinctive clinical pattern of disease described above, then there are several genes of interest but these have not been substantiated due to the issues described above [15][16][17][18] (Table 1; only GWAS with over 1000 cases are included). Lucine zipper protein1 rs94266589 [15,17] PLG Plasminogen * rs4252120 [18]…”

Identification of genetic risk factors of aggressive periodontitis using genomewide association studies in association with those of chronic periodontitis

“…Another study identified plasminogen ( PLG ) SNP, rs4252120, as a shared genetic risk factor for coronary heart disease and AgP with a P ‐value of 5.9 × 10 −5 , an OR of 1.27, and a 95% CI of 1.1‐1.4 through a case‐control replication study 865 German and Dutch cases and 5309 controls, whereas another study showed that PLG SNP rs4252120 showed no association with CP through a case‐control replication study (1419 CP patients and 4562 controls). Notably, a haplotype block downstream of PLG rs1247559 (not in LD with rs4252120) was associated with AgP with a P ‐value of 2.0 × 10 −3 , an OR of 1.33 (851 AgP patients and 6836 controls to adjustment for covariates smoking and sex), and CP with a P ‐value of 2.0 × 10 −2 , and OR of 1.15 (1920 non‐diabetic CP patients + 762 non‐diabetic severe CP patients and 1823 controls) . Analysis of several genomewide data sets of coronary heart disease and AgP revealed that TGF ‐β receptor‐associated protein 1 ( TGFBRAP1 ) SNP, rs2679895, associated with not only AgP [a P ‐value of 1.6 × 10 −3 , OR of 1.27, and 95% CI of 1.09‐1.47 through a case‐control replication study (703 German cases and 2143 controls)] but also coronary heart disease [a P ‐value of 3.0 × 10 −4 , OR of 0.84, and 95% CI of 0.8‐0.9 through a case‐control GWAS (4117 German and Dutch cases and 5824 controls)] .…”