DSIM Årsmødet 6. marts 2009 Arvelighed og Rheumatoid artrit 1

Reumatologiske sygdomme En heterogen gruppe af sygdomme, der almindeligvis afficerer bevægeapparatet (bevægeapparatets medicinske sygdomme)

Reumatologi Degenerative sygdomme Inflammatoriske sygdomme Bløddelsgigt (regionale smertetilstande) Bindevævssygdomme Generaliserede smertetilstande Idrætsskader

Reumatologi Inflammatoriske sygdomme – Polyartritter – Oligoartritter – Monartritter – Spondylartritter – Infektionsrelaterede artritter – Krystalartritter – Sjældne artropatier

5

8

9

10 Pedersen JK, Svendsen AJ, Horslev-Petersen K. Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to Open Rheumatol J 2007; 1: Nov 27.:18-23.

11 Michou L, Rat AC, Lasbleiz S, Bardin T, Cornelis F. Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families. J Rheumatol 2008; 35(5):

12 Jones MA, Silman AJ, Whiting S, Barrett EM, Symmons DP. Occurrence of rheumatoid arthritis is not increased in the first degree relatives of a population based inception cohort of inflammatory polyarthritis. Ann Rheum Dis 1996; 55(2):89-93.

13 Danish 1965 UK-ARC 1970 Finnish 1986 Australian 1992 UK-ARC 1993 Danish 2002 Twin sources Nation-wide Population basedBirth cohort ARA Number of twin pairs includedMZ DZ MZ proportion %Same-sexed 57 (49-64) (24-36) Mix-sexed (14-31) (39-80) 45 (38-52) 27 (15-41) Concordance rates%Pairwise MZ-30(12-54)-21(5-51)15(9-25)- Pairwise DZ-5(2-13)-0(0-34)4(1-9)- Probandwise MZ50(38-64)-22(14-33)--0(0-24) Probandwise DZ5(2-13)-7(4-11)--9(2-24)

14 CHARACTERIZING THE QUANTITATIVE GENETIC CONTRIBUTION TO RHEUMATOID ARTHRITIS USING DATA FROM TWINS Conclusion. Genetic factors have a substantial contribution to RA in the population, accounting for 60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity. MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 2000; 43(1):30-37.

Gregersen, P. K.et al. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum

The contribution of HLA to rheumatoid arthritis Estimates on both population and hospital based data suggest that HLA genes accounts for 37% of genetic contribution to RA 16 Deighton CM, Walker DJ, Griffiths ID, Roberts DF. The contribution of HLA to rheumatoid arthritis. Clin Genet 1989; 36:

17 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447(7145):

Genetic risk factors 18 GenesOdds ratio HeterozygoteHomozygote MHC class II antigens2.36 ( )5.21( ) PTPN221.98( )3.32( ) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447(7145):

RA associerede autoantistoffer Reumafaktorer (1940) Anti-filaggrin antistoffer (AFA) – Antiperinukleære antistoffer (1964) – Antikeratin antistoffer (1979) Anti-CCP antistoffer (2000)

Padyukov, L.et al. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum

21 Vittecoq O et al. Klemmer N. Smoking and inflammatory diseases. Best Pract Res Clin Rheumatol 2008; 22(5):

22 Vittecoq O et al. Klemmer N. Smoking and inflammatory diseases. Best Pract Res Clin Rheumatol 2008; 22(5):

Rheumatoid arthritis We expect more subdivisions to be developed soon when additional biomarkers as well as additional clinically relevant features are identified that associate with different genetic polymorphisms and environmental triggers. 23