ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash and immunological manifestations in patients with systemic lupus erythematosus with European ancestry.
OBJECTIVE
It was hypothesised that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with systemic lupus erythematosus (SLE).


METHODS
To assess genetic association, 2366 patients with SLE and 2931 unaffected controls with European ancestry were analysed. The patients with SLE were coded by the presence or absence of individual American College of Rheumatology criteria. Logistic regression and Pearson chi(2) tests were used to assess statistical significance.


RESULTS
For overall case-control analysis, a highly significant association was detected (p=2.22x10-21, OR 1.73). Using case-only analysis, a significant association was detected with renal criteria (p=0.0003), discoid rash (p=0.02) and immunological criteria (p=0.04). When patients with SLE were compared with healthy controls, the association became stronger for renal (p=4.69x10-22, OR 2.15), discoid (p=1.77x10-14, OR 2.03) and immunological (p=3.49x10-22, OR 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (SLE), 20.4% (renal), 18.1% (immunological) and 19.5% (discoid).


CONCLUSIONS
These results show a strong association between the risk allele (A) at rs1143679 and renal disease, discoid rash and immunological manifestations of SLE.
Kim-Howard
Xana
X
Genetic Epidemiology Unit, Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Maiti
Amit K
AK
Anaya
Juan-Manuel
JM
Bruner
Gail R
GR
Brown
Elizabeth
E
Merrill
Joan T
JT
Edberg
Jeffrey C
JC
Petri
Michelle A
MA
Reveille
John D
JD
Ramsey-Goldman
Rosalind
R
Alarcon
Graciela S
GS
Vyse
Timothy J
TJ
Gilkeson
Gary
G
Kimberly
Robert P
RP
James
Judith A
JA
Guthridge
Joel M
JM
Harley
John B
JB
Nath
Swapan K
SK
D001323:Autoantibodies / Q000097:blood; D039481:CD11b Antigen / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008179:Lupus Erythematosus, Discoid / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008297:Male
D001323:Autoantibodies; D039481:CD11b Antigen; C509295:ITGAM protein, human