Authors | Study Design | Ethnicity | Number Of Patients | Clinical Groups | Analysed Gene Polymorphisms | Analysed Microbes | Associations |
---|---|---|---|---|---|---|---|
Complement System (MBL) | |||||||
Liukkonen A et al. 2017 [31] | CS | Finnish Study Population | 222 | Generalised Periodontitis, Localised Periodontitis, Periodontitis free | MBL2 (allele D, allele B, allele C) Grouped as: wild-type A/A, heterozygote A/O homozygote O/O | Aa P. gingivalis | MBL2 homozygote variant (O/O) type could provoke the virulence of Aa |
TLR | |||||||
Kinane DF et al. 2006 [34] | In vitro | – | HGECs from healthy gingival tissues from 6 healthy subjects | Two HGECs from subjects heterozygous for the TLR4 polymorphism and four with the wild-type TLR4. | TLR4 Asp299Gly and Thr399Ile (Mutant type) TLR4 normal (Wild type) | P. gingivalis | Wild type TLR4 (Normal) appears more responsive to P.gingivalis than the mutant type |
Holla LI et al. 2010 [35] | CC | Caucasian | 481 | CP and H | TLR2 2408G/A, i.e. Arg753Gln and -16934A/T TLR9-1486C/T, -1237C/T and 12848A/G | Aa P. gingivalis P. intermedia T. forsythia T. denticola P. micros F. nucleatum | Not significant |
CD14 | |||||||
Schulz S et al. 2008 [33] | CC | Caucasian | 213 | AgP, CP and H | CD14 -159C > T, TLR4 Asp299Gly, Thr399Ile | P. gingivalis P. intermedia T. forsythia Aa T. denticola | CD14 -159TT genotype + patients: < P. intermedia detection |
Gong Y et al. 2013 [32] | CS | – | 204 | Renal transplant patients with and without cyclosporine A induced gingival overgrowth | CD14–260C > T | P. gingivalis P. intermedia T. forsythia Aa T. denticola | Gingival overgrowth patients with CD14–260 CT + TT: > detection of P. gingivalis, T. forsythia,T. denticola and red complex. |
FcR | |||||||
Kobayashi T et al. 2000 [81] | CC | Japanese | 33 | CP and H | FcγRIIIb-NA1 and FcγRIIIb-NA2 | P.gingivalis | CP patients with both FcγRIIIb-NA1/NA1 and FcγRIIIb-NA2/NA2 genotypes: lower stimulation index for IgG1- and IgG3-mediated phagocytosis in PMNs |
Kaneko S et al. 2004 [41] | CC | Japanese and Caucasian | 185 | AgP | FcαRI nt324 A → G | P. gingivalis | FcαRI nt324 A/A in AgP: decreased phagocytosis of P. gingivalis |
Wolf DL et al. 2006 [36] | CC | Caucasian | 205 | CP and H | FcγRIIIb NA1/NA2, FcγIIa 131R/H | 19 bacterial stains | Not significant |
Nicu EA et al. 2007 [37] | CS | Mixed | 98 | CP | FcγRIIa131H/R | Aa | In CP patients with FcγRIIa (H/H): increased phagocytosis, degraulation and elastase release after stimulation with Aa |
Wang Y et al. 2012 [38] | CC | Japanese | 119 | CP and H (females post delivery) | FcγRIIbnt645 + 25A/G, FcγRIIb-nt646-184A/G,FcγRIIb-1232 T,FcγRIIa-R131H,FcγRIIIaV158F,FcγRIIIb-NA1/NA2 | P. gingivalis P. intermedia Aa | Not significant |
Sugita N et al. 2012 [39] | CS | Japanese | 32 | CP and H | FcγRIIb-nt645 + 25A/G | P.gingivalis | FcγRIIb-nt645 + 25AA genotype: < IgG4 levels produced against P. gingivalis sonicate and IgG2 produced against the P. gingivalis 40-kDa outer membrane protein (OMP) |
IL-1 | |||||||
Socransky SS et al. 2000 [42] | CS | – | 108 | CP | IL-1A + 4845 and IL-1B + 3954 | 40 taxa | IL-1genotype + subjects: > counts of T. forsythia, T. denticola, F.nucleatum, F. periodonticum, Campylobacter gracilis, C. showae, Streptococcus constellatus. Streptococcus intermedius, Streptococcus gordonii and 3 Capnocytophage species |
Cullinan MP et al. 2001 [43] | L | Caucasian | 295 | CP | IL-1a + 4845 and IL-1B + 3954 | Aa P. gingivalis P. intermedia | Not significant |
Papapanou PN et al. 2001 [45] | CC | Caucasian | 205 | CP and H | IL-1A + 4845 and IL-1B + 3953 | 19 bacterial stains | Not significant |
Jansson H et al. 2005 [77] | L | – | 22 | Patients with dental implants | IL-1α-889 and IL-1β + 3953 | P. gingivalis P. nigrescens Aa | Not significant |
Kowalski J et al. 2006 [48] | CS | – | 16 | CP | IL-1A-889 and IL-1B + 3953 | P. gingivalis P. intermedia T. forsythia Aa T. denticola F. nucleatum E. corrodens P. micros C. rectus | IL-1 genotype + subjects: Higher total count of C. Rectus, red complex and orange complex bacteria IL-1genotype - subjects: Higher mean titre of P. intermedia |
Agerbaek MR et al. 2006 [76] | CS | Caucasian | 151 | CP in supportive periodontal therapy | IL-1A + 4845 and IL-1B-3954 | 40 taxa | IL-1 genotype negative subjects: > total bacteria load and > levels of Aa, E. nodatum, P. gingivalis, Streptococcus anginosus |
Kratka Z et al. 2007 [72] | L | – | 20 | AgP | IL-1A -889C/T and IL-1B + 3953C/T | P. gingivalis P. intermedia T. forsythia Aa T. denticola | Not significant |
Ferreira SB et al. 2008 [47] | CC | Mixed | 292 | CP and H | IL-1β 3954 | P. gingivalis T. forsythia Aa T. denticola | Not significant |
Gonçalves L de S et al. 2009 [46] | CC | Mixed | 105 | CP and H (Grouped into HIV on HARRT and non HIV) | IL-1A + 4845 and IL-1B + 3954 | 33 bacterial species | Not significant |
Schulz S et al. 2011 [71] | CC | Caucasian | 248 | AgP, CP and H | IL1α(rs180058),IL-1β (rs16944, rs1143634), IL-1R (rs2234650), and IL-1RA (rs315952) | P. gingivalis P. intermedia T. forsythia Aa T. denticola | Il-1α rs1800587, Il-1β rs 1,143,634 and composite genotype: > Aa detection in AgP group |
Cantore S et al. 2014 [44] | CC | Italian Caucasian | 195 | H and CP | IL-1α + 4845 and IL-1β + 3954 | Subgingival species | Not significant |
Deppe H et al. 2015 [79] | Prospective | Caucasian | 104 | Type 2 diabetes mellitus patients and healthy controls | IL-1A, IL-1B and IL-1RN | Red, orange, green, yellow and purple complexes | Not significant |
IL-2 | |||||||
Reichert S et al. 2009 [49] | CC | Caucasian | 200 | AgP, CP and H | IL-2 -330 T/G and 166 G/T | P. gingivalis P. intermedia T. forsythia Aa T. denticola | IL-2-330, 166 TT-TT haplotype and 166TT: > detection of P. gingivalis and red complex IL-2 -330 TG: < P. gingivalis and red complex |
IL-4 | |||||||
Reichert S et al. 2011 [52] | CC | Caucasian | 243 | AgP, CP and H | IL-4RA Q551R | P. gingivalis P. intermedia T. forsythia Aa T. denticola | QR + RR polymorphism: Presence of T. forsythia |
Finoti LS et al. 2013 [50] | CC | Caucasian | 39 | CP and H | IL-4 -590C/T, +33C/T and VNTR | P. gingivalis T. forsythia T. denticola | IL-4 TCI/CCI haplotype in CP: higher levels of P. gingivalis, T. forsythia, T. denticola |
Bartova J et al. 2014 [51] | CC | – | 62 | CP and H | IL-4 -590c/T and intron 3 VNTR | P. gingivalis P. intermedia T. forsythia Aa | IL-4 -590CC and 11 of IL-4 VNTR: T. forsythia stimulates production of cytokines TNFα, IL-6, IL-10, IFNγ, IL-10, and IL-1β while P. intermedia affects the in vitro production of IL-6 and IL-10 CP. |
IL-6 | |||||||
Nibali L et al. 2007 [68] | CS | Mixed | 45 | AgP | IL-6 -174, Fcα, FcγRIIa, FcγRIIb, FcγRIIIa, FcγRIIIb, FPR, TNF and VDR | Aa P. gingivalis T. forsythia | IL-6- 174GG and Fcγ haplotypes: >Aa detection |
Nibali L et al. 2008 [69] | CS | Mixed | 107 | AgP and CP | IL-1A -889, IL-1B -511, + 3954 IL-6 -174, − 572, − 1363, −1480, − 6106, TLR4–299,-399, TNFα − 308 | Aa P. gingivalis T. forsythia | IL-6 -6106 AA and IL-6 haplotypes (−174G, -572C, − 1363G, -1480C, − 6106A): > detection of Aa |
Nibali L et al. 2010 [57] | CS | Mixed | 40 | CP | IL-6 -174G > C | Aa P. gingivalis | IL-6- 174GG: >Aa detection |
Nibali L et al. 2011 [70] | CS | Indian | 251 | H and with periodontal disease | IL-6 -174, − 572, − 1363, − 6106 and − 1480 | 40 taxa | IL-6- 174GG: > counts of Aa and detection and counts of C. Sputigena |
Nibali L et al. 2013 [82] | L | Caucasian | 12 | AgP | IL-6 -1363, − 1480 | Aa | IL6 haplotype: >counts of Aa before and after treatment |
IL-8 | |||||||
Linhartova PB et al. 2013 [55] | CC | Caucasian | 492 | AgP, CP and H | IL-8 -845C/T, −251A/T, + 396 G/T and + 781C/T | P. gingivalis P. intermedia T. forsythia Aa T. denticola F. nucleatum P. micros | IL8 − 251 T in AgP: > A. actinomycetemcomitans detection CC genotype of IL8 + 781 T/C variant in CP: < T. forsythia detection In non-periodontitis subjects with T allele of IL8 + 396G/T variant or TT genotype: <F. nucleatum detection. |
Finoti LS et al. 2013 [54] | CS | Mixed | 65 | CP and H | IL-8 ATC/TTC | P. gingivalis T. forsythia T. denticola | Not significant |
Finoti LS et al. 2013 [53] | CS | Mixed | 30 | CP and H | IL-8 ATC/TTC and AGT/TTC haplotype | P. gingivalis T. forsythia T. denticola | The diseased sites of AGT/TTC patients: harbour higher levels of P. gingivalis, T. denticola, T. forsythia, and red complex |
IL-10 | |||||||
Reichert S et al. 2008 [56] | CC | Caucasian | 93 | AgP, CP and H | IL-10 -1082G > A, -819C > T and -590C > A | P. gingivalis P. intermedia T. forsythia Aa T. denticola | IL-10 ACC, ATA and ACC/ATA haplotypes: < P. intermedia detection IL-10 GCC/GCC haplotype: > P. intermedia detection |
Luo Y et al. 2013 [78] | CS | Chinese | 202 | Renal transplant patients with and without cyclosporine A induced gingival overgrowth | IL-10 -1082, −819 and − 592 | P. gingivalis P. intermedia T. forsythia Aa T. denticola | Gingival overgrowth patients with ATA haplotype: higher detection and count of P. gingivalis and T. denticola |
IFN-γ & IL-12 | |||||||
Takeuchi-Hatanaka K et al., 2008 [73] | CS | Japanese | 110 | AgP, severe CP, mild CP and H | 5′ flanking region of IL12RB2 | P. gingivalis P. intermedia T. forsythia Aa T. denticola F. nucleatum E. corrodens | Higher serum IgG titres against periodontopathic bacteria in patients with variant alleles |
Reichert S et al. 2008 [58] | CC | Caucasian | 198 | AgP, CP and H | IFN-γ 874 T/A IL-12 1188A/C | P. gingivalis P. intermedia T. forsythia Aa T. denticola | IFN-γ 874AA: < detection of Aa IFN-γ 874TA: > detection of P. intermedia |
Holla LI et al. 2011 [59] | CC | Caucasian | 498 | CP and H | IFN-γ +874A/T | P. gingivalis P. intermedia T. forsythia Aa T. denticola F. nucleatum P. micros | Not significant |
TNFα | |||||||
Schulz S et al. 2008 [60] | CC | Caucasian | 175 | AgP, CP and H | TNFα -308G > A and – 238G > A | P. gingivalis P. intermedia T. forsythia Aa T. denticola | TNFα308GG/238GG haplotype: > P. intermedia detection |
Trombone APF et al. 2009 [62] | CC | Mixed | 304 | CP and H | TNFα -308G/A | P. gingivalis T. forsythia Aa T. denticola | Not significant |
Schulz S et al. 2012 [61] | CS | Caucasian | 942 | Cp and H (All Coronary Artery Disease patients) | TNFα 308G > A and – 238G > A | P. gingivalis P. intermedia T. forsythia Aa T. denticola P. micros F. nucleatum C. rectus E. nodatum E. corrodens C. sputigena | TNFα-308 AG + AA genotype and A-allele: > P. intermedia detection |
HLAII | |||||||
Shimomura-Kuroki J et al. 2009 [74] | CC | Japanese | 64 | AgP, CP and H | IL-1α −889, IL-1α + 4845, IL-1β + 3954 FcγRIIa-H/R131 HLA- DQB1 | P. gingivalis P. intermedia T. forsythia Aa T. denticola | HLADQB1 BamHI sites in patients: > T. forsythia detection |
NF-κβ | |||||||
Schulz S et al. 2010 [75] | CC | Caucasian | 222 | AgP, CP and H | TLR2 (Arg753Gln and Arg677Trp) NF-κβ -94ins/del ATTG | P. gingivalis P. intermedia T. forsythia Aa T. denticola | NF-κβ-94del/del: > Aa detection |
VDR | |||||||
Borges et al. 2009 [64] | CC | Caucasian | 60 | CP and H | VDR TaqI | 38 taxa | Not significant |
T bet | |||||||
Cavalla et al. 2015 [63] | CC | Mixed | 608 | CP, CG and H | TBX21-1993 T/C | P. gingivalis T. forsythia T. denticola | Not significant |
MMP8 | |||||||
Holla LI et al. 2012 [65] | CC | Caucasian | 619 | CP and H | MMP8 (-799C/T and + 17C/G) | P. gingivalis P. intermedia T. forsythia Aa T. denticola P. micros F. nucleatum | Not significant |
ApoE | |||||||
Linhartova PB et al. 2015 [66] | CC | Caucasian | 469 | CP and H | ApoE (rs429358C/T and rs7412C/T) | P. gingivalis P. intermedia T. forsythia Aa T. denticola P. micros F. nucleatum | Not significant |
PPARγ | |||||||
Hirano E et al. 2010 [67] | CS | Japanese | 130 | CP and H All Pregnant Females Grouped as term birth and preterm birth | PPARγPro12Ala | P. gingivalis P. intermedia T. forsythia Aa | Not significant |
GWAS | |||||||
Divaris K et al. 2012 [2] | – | Caucasian and Blacks | 1020 white and 123 African American participants | Healthy to severe chronic periodontitis | 2,178,777 SNPs | C. rectus F. nucleatum P. nigrescens P. gingivalis T. forsythia T. denticola P. intermedia Aa | Not a significant genome wide signals. But 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provide an evidence of association for red and orange complex microbiota, but not for Aa. |
Rhodin K et al. 2014 [25] | – | Caucasian | 1020 + 4504 from two previously conducted GWAs | Healthy to severe chronic periodontitis | 18,307 genes | C. rectus F. nucleatum P. nigrescens P. gingivalis T. forsythia T. denticola P. intermedia Aa | Statistically significant association for 6 genes – 4 with severe chronic periodontitis (NIN, ABHD12B, WHAMM, AP3B2) and 2 with high periodontal pathogen colonisation (red complex – KCNK1, P. gingivalis – DAB2IP). |
Offenbacher S et al. 2016 [10] | – | – | 975 European American For CP in the larger cohort (n = 821 severe CP, 2031 = moderate CP, 1914 = healthy/mild disease) and a German sample of 717 AgP cases and 4210 controls. | Healthy to severe chronic periodontitis and aggressive periodontitis | 21,35,235 SNPs | 8 periodontal pathogens divided into 6 PCTs with distinct microbial community as PCT1 with high pathogen load (Socransky trait), PCT4 with a mixed infection, PCT3, PCT5 dominated by Aa and P. gingivalis, respectively. | Genome-wide significant signals for PCT1 (CLEC19A, TRA, GGTA2P, TM9SF2, IFI16, RBMS3), PCT4 (HPVC1) and PCT5 (SLC15A4, PKP2, SNRPN). Overall, the highlighted loci included genes associated with immune response and epithelial barrier function. |
Systematic review | |||||||
Nibali L et al. 2016 [80] | – | – | 43 studies of candidate genes and two GWAS | Healthy to severe chronic periodontitis and aggressive periodontitis | – | Periodontal Pathogens | No evidence yet that neither IL-1 genetic polymorphisms nor any other investigated genetic polymorphisms are associated with presence and counts of subgingival microbiota. |