A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus.
We identified and replicated an association between ITGAM (CD11b) at 16p11.2 and risk of systemic lupus erythematosus (SLE) in 3,818 individuals of European descent. The strongest association was at a nonsynonymous SNP, rs1143679 (P = 1.7 x 10(-17), odds ratio = 1.78). We further replicated this association in two independent samples of individuals of African descent (P = 0.0002 and 0.003; overall meta-analysis P = 6.9 x 10(-22)). The genetic association between ITGAM and SLE implicates the alpha(M)beta2-integrin adhesion pathway in disease development.
Nath
Swapan K
SK
Genetic Epidemiology Unit, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, Oklahoma 73104, USA. Swapan-Nath@omrf.org
Han
Shizhong
S
Kim-Howard
Xana
X
Kelly
Jennifer A
JA
Viswanathan
Parvathi
P
Gilkeson
Gary S
GS
Chen
Wei
W
Zhu
Cheng
C
McEver
Rodger P
RP
Kimberly
Robert P
RP
Alarcón-Riquelme
Marta E
ME
Vyse
Timothy J
TJ
Li
Quan-Zhen
QZ
Wakeland
Edward K
EK
Merrill
Joan T
JT
James
Judith A
JA
Kaufman
Kenneth M
KM
Guthridge
Joel M
JM
Harley
John B
JB
D020413:3' Untranslated Regions; D001741:Black or African American; D000483:Alleles; D039481:CD11b Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D016001:Confidence Intervals; D005091:Exons; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D044465:White People
D020413:3' Untranslated Regions; D039481:CD11b Antigen; D005819:Genetic Markers; C509295:ITGAM protein, human