• No results found

Genetics, autoantibodies and clinical features in understanding and predicting rheumatoid arthritis

N/A
N/A
Protected

Academic year: 2021

Share "Genetics, autoantibodies and clinical features in understanding and predicting rheumatoid arthritis"

Copied!
7
0
0

Bezig met laden.... (Bekijk nu de volledige tekst)

Hele tekst

(1)

Genetics, autoantibodies and clinical features in understanding and

predicting rheumatoid arthritis

Helm-van Mil, A.H.M. van der

Citation

Helm-van Mil, A. H. M. van der. (2006, October 26). Genetics, autoantibodies and clinical

features in understanding and predicting rheumatoid arthritis. Retrieved from

https://hdl.handle.net/1887/4929

Version:

Corrected Publisher’s Version

License:

Licence agreement concerning inclusion of doctoral thesis in the

Institutional Repository of the University of Leiden

Downloaded from:

https://hdl.handle.net/1887/4929

(2)
(3)



#HA

P

TER¬

!"342!#4

/BJECTIVES¬ 4O¬ ASSESS¬ THE¬ ASSOCIATION¬ BETWEEN¬ THE¬ TUMOR¬ NECROSIS¬ FACTOR¬ RECEPTOR¬ ¬ 4.&2 ¬¬-2¬SINGLE¬NUCLEOTIDE¬POLYMORPHISM¬AND¬RHEUMATOID¬ARTHRITIS¬2! ¬SEVERITY¬ BY¬TAKING¬ADVANTAGE¬OF¬THE¬EXTREMES¬OF¬PHENOTYPES¬THAT¬EXIST¬IN¬ARTHRITIS¬ -ETHODS /UT¬OF¬THE¬,EIDEN¬%ARLY¬!RTHRITIS¬#OHORT¬¬PATIENTS ¬WE¬SELECTED¬PATIENTS THAT¬INITIALLY¬HAD¬THE¬DIAGNOSIS¬OF¬DEl¬NITE¬OR¬PROBABLE¬2!¬ACCORDING¬TO¬!#2¬CRITERIA¬AND DEVELOPED¬COMPLETE¬REMISSION¬¬PATIENTS ¬OR¬HAD¬THE¬WORST¬PROGRESSION¬TO¬DESTRUCTIVE DISEASE¬¬PATIENTS ¬!¬GROUP¬OF¬¬HEALTHY¬CONTROLS¬WAS¬INCLUDED¬)N¬THESE¬GROUPS¬THE 4.&2 GENOTYPE¬WAS¬DETERMINED

2ESULTS¬ 4HE¬ EXTREMES¬ OF¬ PHENOTYPES¬ DID¬ NOT¬ DIFFER¬ SIGNIl¬CANTLY¬ IN¬ GENOTYPE¬ DISTRIBU TION¬.O¬DIFFERENCE¬IN¬GENOTYPE¬DISTRIBUTION¬BETWEEN¬RHEUMATOID¬ARTHRITIS¬PATIENTS¬AND HEALTHY¬CONTROLS¬WAS¬OBSERVED¬

(4)
(5)

 #HA P TER¬ 'ENOTYPING¬OF¬4.&2¬¬-2¬POLYMORPHISM¬WAS¬PERFORMED¬BLINDED ¬BY¬0#2 RESTRIC TION¬FRAGMENT¬POLYMORPHISM¬.A¬))) ¬AS¬PREVIOUSLY¬DESCRIBED¬ ¬4WO¬SAMPLES¬OF¬¬AND¬ ¬PATIENTS¬PROVIDES¬A¬POWER¬OF¬¬TO¬DETECT¬DIFFERENCES¬WITH¬¬CONl¬DENCE¬AND¬AN¬ ODDS¬RATIO¬OF¬¬BASED¬ON¬A¬2¬ALLELE¬FREQUENCY¬OF¬¬4HE¬8 TEST¬WAS¬USED¬TO¬COMPARE¬ THE¬GENOTYPE¬DISTRIBUTION¬BETWEEN¬THE¬TWO¬GROUPS¬OF¬2!¬PATIENTS¬!LL¬ALLELE¬AND¬GENOTYPE FREQUENCIES¬WERE¬IN¬(ARDY¬7EINBERG¬EQUILIBRIUM 2%35,43 4HE¬FREQUENCIES¬OF¬THE¬-¬AND¬2¬ALLELES¬AMONG¬THE¬¬2!¬PATIENTS¬WERE¬¬AND ¬RESPECTIVELY 4ABLE¬¬DEPICTS¬PATIENTS¬CHARACTERISTICS¬AND¬THE¬GENOTYPE¬DISTRIBUTIONS¬ OF¬ BOTH¬ GROUPS¬ OF¬ 2!¬ PATIENTS¬ AND¬ OF¬ THE¬ HEALTHY¬ CONTROLS¬ )N¬ THE¬ REMISSION¬ GROUP ¬ ¬ PATIENTS¬ ¬HAD¬FULl¬LLED¬THE¬!#2 CRITERIA¬FOR¬DEl¬NITE¬2! ¬AND¬¬PATIENTS¬ ¬THE¬ !#2¬ CRITERIA¬ FOR¬ PROBABLE¬ 2!¬ 4HE¬ EXTREMES¬ OF¬ PHENOTYPES¬ DID¬ NOT¬ DIFFER¬ SIGNIl¬CANTLY¬ IN¬ GENOTYPE¬ DISTRIBUTION ¬ AS¬ WELL¬ AS¬ DETERMINED¬ IN¬ THE¬ TOTAL¬ GROUP¬ OF¬ PATIENTS¬ AS¬ WHEN ASSESSED¬IN¬THE¬l¬RST¬HALF¬OF¬PATIENTS¬AND¬REPLICATED¬IN¬THE¬SECOND¬HALF¬)N¬ADDITION ¬THERE WAS¬ NO¬ SIGNIl¬CANT¬ DIFFERENCE¬ IN¬ (EALTH¬ !SSESSMENT¬ 1UESTIONNAIRE¬ AND¬ $ISEASE¬ !CTIVITY¬ 3CORE¬WHEN¬THE¬2¬AND¬-¬ALLELES¬WERE¬COMPARED¬DATA¬NOT¬SHOWN ¬.O¬DIFFERENCE¬ IN¬GENOTYPE¬DISTRIBUTION¬BETWEEN¬RHEUMATOID¬ARTHRITIS¬PATIENTS¬AND¬HEALTHY¬CONTROLS¬WAS

4ABLE¬¬#HARACTERISTICS¬OF¬AND 4.&2 ¬-2¬GENE¬POLYMORPHISM¬IN¬RHEUMATOID¬ARTHRITIS

(6)
(7)

 #HA P TER¬ 2%&%2%.#%3 ¬ ¬ "ARTON¬! ¬*OHN¬3 ¬/LLIER¬7%2 ¬3ILMAN¬! ¬7ORTHINGTON¬*¬!SSOCIATION¬BETWEEN¬RHEUMATOID ARTHRITIS¬AND¬POLYMORPHISM¬OF¬TUMOR¬NECROSIS¬FACTOR¬RECEPTOR¬)) ¬BUT¬NOT¬TUMOR¬NECROSIS¬ FACTOR¬RECEPTOR¬) ¬IN¬CAUCASIANS¬!RTHRITIS¬2HEUM   ¬ ¬ $IEUDϬ0 ¬0ETIT¬% ¬#AILLEAU -OINDRAULT¬3 ¬/SORIO¬* ¬0IERLOT¬# ¬-ARTINEZ¬- ¬ET¬AL¬!SSOCIA TION¬BETWEEN¬TUMOR¬NECROSIS¬FACTOR¬RECEPTOR¬))¬AND¬FAMILIAL¬BUT¬NOT¬SPORADIC¬RHEUMATOID ARTHRITIS ¬%VIDENCE¬FOR¬'ENETIC¬(ETEROGENITY¬!RTHRITIS¬2HEUM¬  ¬ ¬ 'LOSSOP¬ *2 ¬ .IXON¬ ." ¬ $AWES¬ 04 ¬ (ASSELL¬ !" ¬ -ATTEY¬ $,¬ .O¬ ASSOCIATION¬ OF¬ POLYMOR

PHISMS¬IN¬THE¬TUMOR¬NECROSIS¬FACTOR¬RECEPTOR¬)¬AND¬RECEPTOR¬))¬GENES¬WITH¬DISEASE¬SEVERITY¬ IN¬RHEUMATOID¬ARTHRITIS¬*¬2HEUMATOL¬  ¬ ¬ #ONSTANTIN¬! ¬$IEUDE¬0 ¬,AUWERS #ANCES¬6 ¬*AMARD¬" ¬-AZIERES¬" ¬#AMBON 4HOMSON¬! ¬ ET¬AL¬4UMOR¬NECROSIS¬FACTOR¬RECEPTOR¬¬GENE¬POLYMORPHISM¬AND¬SEVERITY¬OF¬RHEUMATOID¬ ARTHRITIS¬!RTHRITIS¬2HEUM¬¬  ¬ ¬ !KEN¬* ¬"ILSEN¬*!- ¬!LLAART¬#& ¬(UIZINGA¬47* ¬"REEDVELD¬&#¬4HE¬,EIDEN¬%ARLY¬!RTHRITIS #LINIC ¬#LIN¬%XP¬2HEUM¬3UPPL¬ 3 3

¬ ¬ !L !NSARI¬ !3 ¬ /LLIER¬ 7% ¬ 6ILLARREAL¬ * ¬ /RDI¬ * ¬ 4EH¬ ,3 ¬ (AJEER¬ !(¬ 4UMOR¬ NECROSIS¬ FACTOR¬ RECEPTOR¬))¬4.&2)) ¬EXON¬¬POLYMORPHISM¬IN¬SYSTEMIC¬LUPUS¬ERYTHEMATOSUS¬4ISSUE¬!N TIGENS¬ 

¬ ¬ +ALTENHËUSER¬3 ¬7AGNER¬5 ¬3CHUSTER¬% ¬7ASSMUTH¬2 ¬3EIDEL¬7 ¬4RÚZLSCH¬- ¬ET¬AL¬)MMUNO GENETIC¬MARKERS¬AND¬SEROPOSITIVITY¬PREDICT¬RADIOLOGICAL¬PROGRESSION¬IN¬EARLY¬RHEUMATOID ARTHRITIS¬INDEPENDENT¬OF¬DISEASE¬ACTIVITY¬*¬2HEUMATOL¬ 

¬ ¬ &ABRIS¬ - ¬ 4OLUSSO¬ " ¬ $I¬ 0OL¬ % ¬ !SSALONI¬ 2 ¬ 3INIGAGLIA¬ , ¬ &ERRACCIOLI¬ '¬ 4UMOR¬ NECROSIS FACTOR ALPHA¬RECEPTOR¬TWO¬POLYMORPHISM¬IN¬PATIENTS¬FROM¬SOUTHERN¬%UROPE¬WITH¬MILD MODERATE¬AND¬SEVERE¬RHEUMATOID¬ARTHRITIS¬*¬2HEUMATOL¬ 

¬ ¬ $AHLQVIST¬32 ¬

EXON¬ ¬AND¬INTERLEUKIN ¬  ¬GENE¬POLYMORPHISMS¬ARE¬NOT¬ASSOCIATED¬WITH¬FAMILY HISTORY¬ BUT¬ TUMOR¬ NECROSIS¬ FACTOR¬ RECEPTOR¬ TYPE¬ ))¬ IS¬ ASSOCIATED¬ WITH¬ HYPERTENSION¬ IN¬ PATIENTS¬WITH¬RHEUMATOID¬ARTHRITIS¬IN¬PATIENTS¬FROM¬NORTHERN¬3WEDEN¬!RTHRITIS¬2HEUM  

Referenties

GERELATEERDE DOCUMENTEN

$2"¬ TYPING¬ WAS¬ PERFORMED¬ IN¬ ¬ 2!¬ PATIENTS¬ FROM¬ THE¬ ,EIDEN¬ %ARLY¬ !RTHRITIS¬ #LINIC¬ THE¬ ,EIDEN¬ %!#¬ A¬ $UTCH¬ POPULATION BASED¬ INCEPTION¬ COHORT¬

$2¬IS¬ASSOCIATED¬WITH¬ANTI ##0 NEGATIVE¬ARTHRITIS¬AND¬NOT¬WITH¬ANTI ##0 POSITIVE¬ ARTHRITIS¬ 4HESE¬ DATA¬ SHOW¬ THAT¬ DISTINCT¬ GENETIC¬ RISK¬ FACTORS¬ ARE¬

¬BUT¬ STRATIl¬CATION¬ REVEALED¬ THAT¬ THE¬ INTERACTION¬ PRIMARILY¬ ASSOCIATES¬ WITH¬ THE¬ ANTI ##0¬

¬IT¬WAS¬OBSERVED¬BY¬TWO¬DIFFERENT¬ METHODS¬ LINKAGE¬ AND¬ ASSOCIATION¬ ANALYSIS ¬ THAT¬ THE¬ 3% ALLELES¬ ARE¬ ONLY¬ A¬ RISK¬ FACTOR¬ FOR¬ 2!¬ THAT¬ IS¬

WERE¬ PROMPTLY¬ TREATED¬ WITH¬ EITHER¬ METHOTREXATE¬ OR¬ SALAZOPYRINE¬ EARLY¬ TREATMENT ¬ 4HE¬

DIFFERENT¬ SAMPLES¬ WERE¬ OBTAINED¬ FROM¬ TWO¬ DIFFERENT¬ JOINTS¬ 4HE¬ DIFFERENCES¬ IN¬ INVASIVE NESS¬ WITHIN¬ THE¬ DIFFERENT¬ SAMPLES¬ OF¬ INDIVIDUAL¬ PATIENTS¬

)N¬CONCLUSION ¬THE¬PRESENT¬STUDY¬OBSERVED¬AFTER¬CORRECTION¬FOR¬DIFFERENCES¬IN¬DISEASE¬DURA TION¬ AND¬ AUTOANTIBODY¬ STATUS¬ AN¬ INCREASE¬ IN¬ VARIATION¬

MODELS¬ THAT¬ TAKE¬ INTO¬ ACCOUNT¬ BOTH¬ GENETIC¬ AND¬ CLINICAL¬ CHARACTERISTICS¬ WILL¬ HAVE¬ TO¬ BE EVALUATED¬ IN¬ PATIENT¬ GROUPS¬ WITH¬ UNDIFFERENTIATED¬