Microsoft Word - Ann 2016.docx


	
  

Vol	
  4,	
  No	
  1	
  (2016)	
  
ISSN	
  2167-­‐8677	
  (online)	
  

DOI	
  10.5195/d3000.2016.47	
  	
  

	
  

	
  

	
  

http://dentistry3000.pitt.edu	
  

	
   New	
  articles	
  in	
  this	
  journal	
  are	
  licensed	
  under	
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  Creative	
  Commons	
  Attribution	
  4.0	
  United	
  States	
  License.	
  

	
  
This	
  journal	
  is	
  published	
  by	
  the	
  University	
  Library	
  System,	
  University	
  of	
  Pittsburgh	
  as	
  part	
  of	
  its	
  D-­‐Scribe	
  Digital	
  Publishing	
  Program	
  and	
  is	
  cosponored	
  
by	
  the	
  University	
  of	
  Pittsburgh	
  Press.	
  

	
  

Orthodontic	
  treatment	
  as	
  a	
  possible	
  trigger	
  of	
  periodontal	
  disease	
  	
  
Ann	
  Lin1	
  
	
  
1	
  University	
  of	
  Pi.sburgh	
  School	
  of	
  Dental	
  Medicine,	
  Pi.sburgh	
  PA,	
  USA

Abstract	
  

Background:	
  Periodontal	
  disease	
  leads	
  to	
  the	
  deteriora.on	
  of	
  oral	
  health,	
  includ-­‐
ing	
   loss	
   of	
   teeth	
   and	
   its	
   suppor1ng	
   structures.	
   It	
   has	
   been	
   established	
   that	
   the	
  
cause	
  of	
  this	
  disease	
  is	
  mul/factorial,	
  indica/ng	
  that	
  both	
  genes	
  and	
  environmen-­‐
tal	
  factors	
  are	
  intertwined	
  with	
  the	
  forma1on	
  and	
  progression	
  of	
  periodontal	
  dis-­‐
ease.	
  Case	
  Descrip+on:	
  Here	
  we	
  discuss	
   the	
  possibility	
  of	
  orthodon4c	
   treatment	
  
serving	
   as	
   a	
   trigger	
   to	
   an	
   early	
   development	
   of	
   periodontal	
   disease	
   in	
   a	
   pa2ent	
  
who	
  has	
   a	
   family	
   history	
   of	
   periodon22s.	
   Between	
  debonding	
   at	
   age	
   17.5	
   years	
  
and	
   age	
   28,	
   the	
   pa-ent	
   experienced	
   gradual	
   general	
   loss	
   of	
   a2achment	
   on	
   the	
  
mandibular	
  arch	
  with	
   the	
   le0	
  mandibular	
  canine	
  having	
  exaggerated	
  a4achment	
  
loss.	
   Between	
  age	
  28	
  and	
  29	
   years,	
   the	
  pa6ent	
  experienced	
  exacerbated	
   loss	
  of	
  
a!achment	
  at	
  both	
  mandibular	
  canines.	
  Prac#cal	
  Implica#ons:	
  The	
  occurrence	
  of	
  
a"achment	
  loss	
  during	
  and	
  a2er	
  orthodon3c	
  treatment	
  should	
  not	
  be	
  overlooked.	
  
It	
  is	
  crucial	
  for	
  orthodon0sts	
  to	
  obtain	
  a	
  family	
  history	
  of	
  periodontal	
  disease	
  and	
  
carefully	
  monitor	
  pa0ent’s	
  periodontal	
  condi0ons	
  throughout	
  the	
  treatment.	
  	
  

	
  

Cita%on:	
  Lin,	
  A.	
  (2016)	
  Orthodon(c	
  Treatment	
  
as	
  a	
  Possible	
  Trigger	
  of	
  Periodontal	
  Disease.	
  
Den$stry	
  3000.	
  1:a001	
  
doi:10.5195/d3000.2016.47	
  
Received:	
  May	
  1,	
  2016	
  
Accepted:	
  	
  May	
  5,	
  2016	
  
Published:	
  	
  June	
  7,	
  2016	
  
Copyright:	
  ©2016	
  Lin	
  A.	
  This	
   is	
   an	
  open	
  access	
  
ar!cle	
   licensed	
   under	
   a	
   Crea+ve	
   Commons	
  
A!ribu%on	
  Work	
  4.0	
  United	
  States	
  License.	
  
Email:	
  apl22@pi'.edu

	
  

Introduction	
  

It	
  has	
  been	
  shown	
  that	
  per-­‐
iodontal	
  disease,	
  to	
  be	
  more	
  spe-­‐
cific,	
  periodontitis,	
  affects	
  30-­‐50%	
  
of	
  the	
  population	
  in	
  the	
  United	
  
States	
  [1].	
  This	
  disease	
  is	
  triggered	
  
by	
  the	
  imbalance	
  of	
  local	
  factors,	
  
i.e.	
  bacteria	
  in	
  the	
  oral	
  cavity,	
  and	
  
systemic	
  conditions	
  of	
  the	
  individ-­‐
ual.	
  Despite	
  its	
  etiology	
  being	
  bac-­‐
terial	
  infection	
  such	
  as	
  Aggregati-­‐
bacter	
  actinomycetemcomitans,	
  
Porphyromonas	
  gingivalis,	
  
Prevotella	
  intermedius,	
  etc.,	
  other	
  
factors	
  such	
  as	
  familial	
  aggrega-­‐
tion	
  including	
  genetic	
  and	
  envi-­‐
ronmental	
  elements	
  play	
  a	
  major	
  
role	
  in	
  the	
  development	
  of	
  perio-­‐
dontal	
  disease.	
  

Signs	
  and	
  symptoms	
  of	
  ear-­‐
ly	
  stage	
  periodontal	
  disease	
  (i.e.	
  
gingivitis)	
  will	
  progress	
  to	
  the	
  
more	
  advanced	
  periodontitis	
  if	
  a	
  
patient	
  is	
  susceptible	
  to	
  periodon-­‐
tal	
  disease	
  in	
  aspects	
  of	
  genetics,	
  
local	
  factors	
  in	
  the	
  oral	
  cavity,	
  oral	
  
hygiene,	
  environment,	
  systemic	
  
health	
  conditions,	
  etc.	
  Alveolar	
  
bone	
  and	
  teeth	
  loss	
  are	
  the	
  end	
  
results	
  of	
  periodontal	
  disease	
  if	
  
left	
  untreated	
  or	
  unattended.	
  
Teeth	
  loss	
  due	
  to	
  periodontal	
  dis-­‐
ease	
  has	
  detrimental	
  effects	
  be-­‐
cause	
  the	
  patient	
  may	
  not	
  be	
  the	
  
best	
  candidate	
  for	
  complete	
  den-­‐
tures	
  due	
  to	
  lack	
  of	
  mechanical	
  
support	
  and	
  retention	
  from	
  the	
  
resorbed	
  alveolar	
  ridges.	
  Dental	
  
implants	
  placed	
  in	
  periodontal	
  pa-­‐

tients	
  may	
  not	
  have	
  the	
  desired	
  
success	
  or	
  survival	
  rate	
  [2].	
  	
  

Periodontal	
  disease	
  has	
  se-­‐
rious	
  implications	
  not	
  only	
  be-­‐
cause	
  a	
  continuous	
  bone	
  loss	
  will	
  
eventually	
  lead	
  tooth	
  loss	
  but	
  also	
  
because	
  it	
  is	
  a	
  risk	
  factor	
  for	
  cardi-­‐
ovascular	
  disease	
  and	
  other	
  major	
  
systemic	
  diseases	
  such	
  as	
  diabetes	
  
mellitus.	
  It	
  has	
  been	
  investigated	
  
that	
  periodontal	
  patients	
  may	
  be	
  
low	
  in	
  their	
  neutrophil	
  cell	
  counts	
  
and/or	
  dysfunction	
  of	
  neutrophils	
  
so	
  that	
  the	
  body	
  cannot	
  provide	
  
protection	
  to	
  the	
  periodontium	
  
against	
  bacteria	
  [1].	
  	
  



	
  	
  Orthodon(c	
  treatment	
  as	
  a	
  possible	
  trigger	
  of	
  periodontal	
  disease	
  

Vol	
  4,	
  No	
  1	
  (2016)	
  	
  	
  	
  DOI	
  10.5195/d3000.2016.47	
  

	
  http://dentistry3000.pitt.edu	
  
2	
  

Having	
  atherosclerotic	
  
problems	
  already,	
  cardiovascular	
  
patients	
  are	
  further	
  in	
  danger	
  
since	
  bacteria	
  contributing	
  to	
  per-­‐
iodontal	
  disease	
  such	
  as	
  Strepto-­‐
coccus	
  sanguis	
  and	
  Porphyromo-­‐
nas	
  gingivalis	
  can	
  enter	
  the	
  blood	
  
stream	
  and	
  can	
  adhere	
  to	
  athero-­‐
sclerotic	
  plaques	
  inducing	
  blood	
  
clots.	
  Patients	
  with	
  diabetes	
  are	
  at	
  
an	
  increased	
  risk	
  of	
  developing	
  
periodontal	
  disease	
  because	
  of	
  the	
  
increase	
  in	
  pro-­‐inflammatory	
  cy-­‐
tokines	
  such	
  as	
  TNF-­‐α	
  	
  that	
  will	
  
increase	
  the	
  host	
  response	
  to	
  per-­‐
iodontal	
  pathogens	
  and	
  conse-­‐
quently,	
  the	
  host	
  tissue	
  itself.	
  	
  

	
   Given	
  the	
  inconveniences	
  
and	
  detrimental	
  life-­‐changing	
  ef-­‐
fects	
  this	
  disease	
  brings	
  towards	
  
its	
  patients,	
  more	
  emphasis	
  in	
  the	
  
research	
  to	
  elucidate	
  the	
  mecha-­‐
nisms	
  and	
  treatments	
  of	
  periodon-­‐
tal	
  disease	
  should	
  be	
  given.	
  Genet-­‐
ic	
  testing	
  at	
  an	
  early	
  age	
  could	
  
help	
  patients	
  with	
  their	
  choice	
  of	
  

lifestyle.	
  If	
  done	
  appropriately,	
  
genetic	
  testing	
  can	
  also	
  help	
  pa-­‐
tients	
  avoid	
  potential	
  triggers	
  of	
  
periodontal	
  disease	
  in	
  life,	
  which	
  
we	
  discuss	
  in	
  this	
  report.	
   	
  

Orthodontic	
  Treatent	
  Triggering	
  
Localized	
  Bone	
  Loss	
  

Here	
  we	
  describe	
  a	
  case	
  of	
  
a	
  female	
  patient	
  who	
  presented	
  
with	
  generalized	
  mandibular	
  bone	
  
loss	
  in	
  her	
  late	
  20s.	
  The	
  patient	
  
had	
  bilateral	
  maxillary	
  canines	
  
slightly	
  overlapping	
  lateral	
  incisors	
  
creating	
  crowding	
  of	
  the	
  four	
  
teeth	
  after	
  the	
  eruption	
  of	
  perma-­‐
nent	
  teeth	
  and	
  therefore	
  received	
  
orthodontic	
  treatment	
  at	
  age	
  16	
  
when	
  she	
  was	
  in	
  a	
  Taiwanese	
  high	
  
school.	
  Prior	
  to	
  the	
  orthodontic	
  
treatment,	
  the	
  patient	
  had	
  no	
  
signs	
  of	
  periodontal	
  disease;	
  how-­‐
ever,	
  her	
  father	
  began	
  to	
  manifest	
  
signs	
  of	
  bone	
  loss	
  during	
  his	
  col-­‐
lege	
  years,	
  suggesting	
  a	
  familial	
  
susceptibility.	
  

The	
  first	
  trigger	
  

The	
  patient	
  had	
  orthodon-­‐
tic	
  brackets	
  for	
  16	
  months	
  and	
  
during	
  the	
  course	
  of	
  the	
  treat-­‐
ment,	
  she	
  reported	
  to	
  her	
  ortho-­‐
dontist	
  that	
  she	
  was	
  aware	
  that	
  
her	
  gum	
  lines	
  had	
  receded	
  slightly	
  
on	
  her	
  right	
  maxillary	
  central	
  inci-­‐
sor	
  and	
  the	
  mandibular	
  anterior	
  
teeth.	
  Her	
  orthodontist	
  confirmed	
  
her	
  observation	
  but	
  did	
  not	
  men-­‐
tion	
  how	
  he	
  would	
  proceed	
  on	
  
managing	
  the	
  receding	
  gingiva.	
  He	
  
simply	
  stated	
  that	
  there	
  is	
  nothing	
  
he	
  can	
  do	
  and	
  “gums	
  do	
  not	
  grow	
  
back,	
  once	
  they	
  are	
  lost,	
  they	
  are	
  
gone	
  forever.”	
  Disheartened,	
  the	
  
patient	
  tried	
  to	
  move	
  past	
  the	
  de-­‐
pressing	
  news.	
  After	
  debonding	
  of	
  
orthodontic	
  brackets,	
  the	
  patient	
  
was	
  instructed	
  to	
  wear	
  upper	
  and	
  
lower	
  arch	
  removable	
  retainers	
  
during	
  sleep.	
  She	
  was	
  never	
  given	
  
an	
  option	
  of	
  placing	
  a	
  lingual	
  bar	
  
on	
  her	
  mandibular	
  anterior	
  teeth.	
  	
  

The	
  patient	
  noticed	
  that	
  af-­‐
ter	
  debonding	
  and	
  a	
  period	
  of	
  
time	
  wearing	
  her	
  lower	
  retainer,	
  
her	
  mandibular	
  left	
  canine	
  be-­‐
came	
  more	
  tipped	
  towards	
  the	
  
lingual.	
  In	
  addition,	
  whenever	
  she	
  
worn	
  her	
  mandibular	
  retainer,	
  
pain	
  and	
  strain	
  on	
  teeth	
  occurred	
  
in	
  her	
  entire	
  arch,	
  with	
  the	
  dis-­‐
comfort	
  exaggerated	
  on	
  the	
  left	
  
mandibular	
  canine.	
  She	
  reported	
  
this	
  to	
  her	
  orthodontist;	
  however,	
  
reliefing	
  the	
  wires	
  that	
  rested	
  on	
  
the	
  left	
  mandibular	
  canine	
  did	
  not	
  
show	
  any	
  improvement.	
  The	
  pa-­‐
tient	
  still	
  had	
  discomfort	
  and	
  
eventually	
  discontinued	
  the	
  use	
  of	
  
retainers	
  after	
  5	
  years.	
  Over	
  the	
  
course	
  of	
  10	
  years	
  after	
  debond-­‐
ing,	
  the	
  patient	
  noticed	
  the	
  slow	
  



	
  	
  Orthodon(c	
  treatment	
  as	
  a	
  possible	
  trigger	
  of	
  periodontal	
  disease	
  

Vol	
  4,	
  No	
  1	
  (2016)	
  	
  	
  	
  DOI	
  10.5195/d3000.2016.47	
  

	
  http://dentistry3000.pitt.edu	
  
3	
  

progression	
  of	
  gingival	
  recession	
  
on	
  the	
  mandibular	
  anterior	
  teeth.	
  

The	
  second	
  trigger:	
  stress	
  

At	
  age	
  28,	
  the	
  patient	
  be-­‐
gan	
  professional	
  school	
  and	
  during	
  
the	
  intense	
  and	
  stressful	
  first	
  year	
  
of	
  courses,	
  she	
  noticed	
  that	
  her	
  
entire	
  mandibular	
  arch	
  had	
  gingi-­‐
val	
  recession	
  in	
  addition	
  to	
  pro-­‐
gressive	
  attachment	
  loss	
  on	
  the	
  
mandibular	
  canines.	
  At	
  age	
  29	
  and	
  
second	
  year	
  of	
  studies,	
  she	
  decid-­‐
ed	
  that	
  she	
  would	
  be	
  seeking	
  per-­‐
iodontal	
  treatment.	
  

Family	
  history	
  

The	
  patient’s	
  father,	
  now	
  
59	
  years	
  old,	
  had	
  begun	
  develop-­‐
ing	
  periodontal	
  problems	
  since	
  
college.	
  His	
  father	
  (the	
  patient’s	
  
grandfather)	
  had	
  complete	
  den-­‐
tures	
  by	
  age	
  65.	
  He	
  got	
  his	
  teeth	
  

cleaned	
  for	
  the	
  first	
  time	
  in	
  col-­‐
lege,	
  at	
  age	
  20,	
  and	
  reported	
  “af-­‐
ter	
  the	
  hygienist	
  got	
  rid	
  of	
  my	
  cal-­‐
culus,	
  I	
  felt	
  that	
  my	
  teeth	
  became	
  
loose	
  and	
  a	
  little	
  wobbly.”	
  Later	
  in	
  
graduate	
  school,	
  at	
  age	
  22,	
  he	
  
picked	
  up	
  the	
  habit	
  of	
  smoking	
  
because	
  of	
  the	
  stress	
  to	
  which	
  he	
  
was	
  subjected.	
  He	
  reports	
  that	
  he	
  
does	
  not	
  remember	
  if	
  he	
  began	
  to	
  
notice	
  bone	
  loss	
  around	
  his	
  teeth	
  
but	
  at	
  age	
  of	
  35	
  during	
  a	
  visit	
  to	
  a	
  
dental	
  office,	
  he	
  was	
  diagnosed	
  
with	
  moderate	
  periodontitis.	
  The	
  
patient’s	
  father	
  kept	
  his	
  condition	
  
under	
  control	
  and	
  has	
  not	
  lost	
  
teeth	
  since	
  his	
  diagnosis.	
  The	
  pa-­‐
tient’s	
  mother	
  does	
  not	
  have	
  peri-­‐
odontal	
  disease.	
  

Discussion	
  

This	
  case	
  illustrates	
  perio-­‐
dontal	
  bone	
  loss	
  triggered	
  by	
  or-­‐

thodontic	
  movement	
  and/or	
  
stress	
  aggregating	
  in	
  the	
  same	
  
family.	
  Periodontitis	
  aggregates	
  in	
  
this	
  family	
  (Figure	
  1)	
  in	
  an	
  appar-­‐
ent	
  autosomal	
  dominant	
  mode	
  of	
  
inheritance	
  since	
  the	
  father	
  (and	
  
possibly	
  the	
  grandfather)	
  poten-­‐
tially	
  had	
  periodontitis	
  and	
  the	
  
patient,	
  a	
  potential	
  third	
  genera-­‐
tion	
  case,	
  also	
  manifests	
  signs	
  of	
  
bone	
  and	
  attachment	
  loss.	
  

Previous	
  studies	
  [3,4]	
  have	
  
suggested	
  familial	
  aggregation	
  in	
  
early	
  onset	
  periodontitis.	
  It	
  was	
  
also	
  suggested	
  that	
  autosomal	
  
recessive	
  genes	
  and	
  environmen-­‐
tal	
  factors	
  were	
  responsible	
  for	
  
the	
  transmission	
  of	
  the	
  disease	
  in	
  
early	
  onset	
  periodontitis	
  due	
  to	
  
the	
  shared	
  genes	
  among	
  biologic	
  
family	
  and	
  possible	
  saliva	
  trans-­‐
mission	
  of	
  bacteria	
  such	
  as	
  Ag-­‐
gregatibacter	
  actinomycetem-­‐
comitans	
  [3].	
  A	
  report	
  of	
  monozy-­‐
gotic	
  twins	
  [4]	
  	
  strongly	
  suggested	
  
that	
  adult	
  chronic	
  periodontitis	
  is	
  
influenced	
  by	
  genetic	
  and	
  envi-­‐
ronment	
  factors,	
  although	
  there	
  is	
  
the	
  notion	
  that	
  early	
  family	
  envi-­‐
ronment	
  plays	
  less	
  of	
  a	
  significant	
  
role	
  [5].	
  Recent	
  studies	
  have	
  indi-­‐
cated	
  that	
  the	
  Interleukin-­‐1	
  (IL1)	
  
gene	
  serves	
  as	
  an	
  important	
  regu-­‐
lator	
  for	
  the	
  expression	
  of	
  perio-­‐
dontitis.	
  Both	
  the	
  T	
  allele	
  of	
  
rs17561	
  of	
  IL1-­‐αα	
  and	
  IL1-­‐βββββ	
  	
  
rs1143634	
  T	
  allele	
  are	
  positively	
  
associated	
  with	
  periodontitis	
  [6].	
  
Other	
  polymorphisms	
  of	
  IL1-­‐α	
  	
  
were	
  also	
  shown	
  to	
  have	
  an	
  asso-­‐
ciation	
  with	
  moderate	
  to	
  severe	
  
periodontitis	
  across	
  different	
  eth-­‐
nicities	
  [7].	
  	
  

This	
  case	
  report	
  substanti-­‐
ates	
  that	
  periodontal	
  disease	
  is	
  of	
  



	
  	
  Orthodon(c	
  treatment	
  as	
  a	
  possible	
  trigger	
  of	
  periodontal	
  disease	
  

Vol	
  4,	
  No	
  1	
  (2016)	
  	
  	
  	
  DOI	
  10.5195/d3000.2016.47	
  

	
  http://dentistry3000.pitt.edu	
  
4	
  

multifactorial	
  inheritance.	
  Since	
  
one	
  of	
  the	
  risks	
  of	
  orthodontic	
  
treatment	
  is	
  the	
  development	
  of	
  
periodontal	
  loss,	
  it	
  is	
  not	
  possible	
  
to	
  determine	
  exactly	
  whether	
  it	
  
was	
  the	
  treatment	
  or	
  the	
  genetic	
  
factor	
  that	
  caused	
  bone	
  loss.	
  A	
  
synergistic	
  effect	
  of	
  the	
  two	
  fac-­‐
tors	
  could	
  be	
  a	
  possible	
  factor	
  that	
  
contributed	
  to	
  the	
  onset	
  of	
  the	
  
periodontal	
  problems	
  the	
  patient	
  
presented	
  here	
  had.	
  However,	
  it	
  is	
  
worth	
  noticing	
  that	
  there	
  was	
  only	
  
localized	
  bone	
  or	
  attachment	
  loss	
  
of	
  buccal	
  of	
  the	
  left	
  mandibular	
  
canine	
  after	
  debonding	
  and	
  no	
  
signs	
  of	
  generalized	
  attachment	
  
loss	
  in	
  the	
  mandible	
  or	
  maxilla.	
  
Between	
  debonding	
  and	
  entering	
  
professional	
  school,	
  a	
  10-­‐year	
  gap,	
  
the	
  patient	
  reported	
  remembering	
  
gradual	
  loss	
  of	
  attachment	
  on	
  the	
  
posterior	
  mandibular	
  teeth.	
  	
  

During	
  the	
  first	
  year	
  in	
  pro-­‐
fessional	
  school,	
  the	
  patient	
  began	
  
to	
  notice	
  rapid	
  attachment	
  loss	
  on	
  
the	
  mandibular	
  incisors	
  showing	
  
cementum	
  on	
  the	
  buccal	
  aspect	
  of	
  
the	
  teeth	
  and	
  the	
  anterior	
  teeth	
  
became	
  sensitive	
  to	
  cold	
  where	
  
the	
  cementum-­‐enamel	
  junction	
  
was	
  exposed	
  (Figure	
  2).	
  These	
  
signs	
  and	
  symptoms	
  all	
  indicate	
  
that	
  the	
  environment	
  factor	
  (i.e.,	
  
orthodontic	
  treatment	
  in	
  adoles-­‐
cence	
  and	
  stressful	
  life)	
  deter-­‐
mined	
  the	
  course	
  of	
  the	
  disease	
  in	
  
addition	
  to	
  the	
  possible	
  variable	
  
IL1	
  gene	
  expression	
  of	
  the	
  patient.	
  

References	
  

1.	
  Newman	
  MG,	
  Takei	
  HH,	
  
Klokkevold	
  PR,	
  Carranza	
  FA.	
  
(2016).	
  Carranza’s	
  Clinical	
  Perio-­‐
dontology.	
  

2.	
  Dental	
  implants	
  in	
  the	
  perio-­‐
dontal	
  patient.	
  Greenstein	
  G,	
  Ca-­‐
vallaro	
  J	
  Jr,	
  Tarnow	
  D.	
  Dent	
  Clin	
  
North	
  Am.	
  2010	
  Jan;54(1):113-­‐28.	
  
doi:	
  10.1016/j.cden.2009.08.008.	
  
Review.	
  PMID:20103475	
  

3.	
  Familial	
  aggregation	
  of	
  perio-­‐
dontal	
  indices.	
  Beaty	
  TH,	
  Colyer	
  
CR,	
  Chang	
  YC,	
  Liang	
  KY,	
  Graybeal	
  
JC,	
  Muhammad	
  NK,	
  Levin	
  LS.	
  J	
  
Dent	
  Res.	
  1993	
  Feb;72(2):544-­‐51.	
  
PMID:8423252	
  

4.	
  Chronic	
  periodontitis	
  with	
  famil-­‐
ial	
  aggregation	
  and	
  discordant	
  
identical	
  twins.	
  Grech	
  SC.	
  Dentis-­‐
try	
  3000	
  2015;	
  3(1).	
  Doi:	
  
10.5195/d3000.2015.30	
  

5.	
  Genetic	
  and	
  inheritance	
  consid-­‐
erations	
  in	
  periodontal	
  disease.	
  

Michalowicz	
  BS.	
  Curr	
  Opin	
  Perio-­‐
dontol.	
  1993:11-­‐7.	
  Review.	
  
PMID:8401833	
  

6.	
  Association	
  between	
  IL-­‐1α	
  
rs17561	
  and	
  IL-­‐1β	
  rs1143634	
  pol-­‐
ymorphisms	
  and	
  periodontitis:	
  a	
  
meta-­‐analysis.	
  Yin	
  WT,	
  Pan	
  YP,	
  Lin	
  
L.	
  Genet	
  Mol	
  Res.	
  2016	
  Feb	
  
5;15(1).	
  doi:	
  
10.4238/gmr.15017325.	
  
PMID:26909953	
  

7.	
  Association	
  of	
  interleukin-­‐1	
  
gene	
  variations	
  with	
  moderate	
  to	
  
severe	
  chronic	
  periodontitis	
  in	
  
multiple	
  ethnicities.	
  Wu	
  X,	
  Offen-­‐
bacher	
  S,	
  Lόpez	
  NJ,	
  Chen	
  D,	
  Wang	
  
HY,	
  Rogus	
  J,	
  Zhou	
  J,	
  Beck	
  J,	
  Jiang	
  S,	
  
Bao	
  X,	
  Wilkins	
  L,	
  Doucette-­‐Stamm	
  
L,	
  Kornman	
  K.	
  J	
  Periodontal	
  Res.	
  
2015	
  Feb;50(1):52-­‐61.	
  doi:	
  
10.1111/jre.12181.	
  Epub	
  2014	
  Apr	
  
2.	
  PMID:24690098