Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction.
Osteopontin (SPP1) is an important bone matrix mediator found to have key roles in inflammation and immunity. SPP1 genetic polymorphisms and increased osteopontin protein levels have been reported to be associated with SLE in small patient collections. The present study evaluates association between SPP1 polymorphisms and SLE in a large cohort of 1141 unrelated SLE patients [707 European-American (EA) and 434 African-American (AA)], and 2009 unrelated controls (1309 EA and 700 AA). Population-based case-control association analyses were performed. To control for potential population stratification, admixture adjusted logistic regression, genomic control (GC), structured association (STRAT), and principal components analysis (PCA) were applied. Combined analysis of 2 ethnic groups, showed the minor allele of 2 SNPs (rs1126616T and rs9138C) significantly associated with higher risk of SLE in males (P = 0.0005, OR = 1.73, 95% CI = 1.28-2.33), but not in females. Indeed, significant gene-gender interactions in the 2 SNPs, rs1126772 and rs9138, were detected (P = 0.001 and P = 0.0006, respectively). Further, haplotype analysis identified rs1126616T-rs1126772A-rs9138C which demonstrated significant association with SLE in general (P = 0.02, OR = 1.30, 95%CI 1.08-1.57), especially in males (P = 0.0003, OR = 2.42, 95%CI 1.51-3.89). Subgroup analysis with single SNPs and haplotypes also identified a similar pattern of gender-specific association in AA and EA. GC, STRAT, and PCA results within each group showed consistent associations. Our data suggest SPP1 is associated with SLE, and this association is especially stronger in males. To our knowledge, this report serves as the first association of a specific autosomal gene with human male lupus.
Han
Shizhong
S
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
Guthridge
Joel M
JM
Harley
Isaac T W
IT
Sestak
Andrea L
AL
Kim-Howard
Xana
X
Kaufman
Kenneth M
KM
Namjou
Bahram
B
Deshmukh
Harshal
H
Bruner
Gail
G
Espinoza
Luis R
LR
Gilkeson
Gary S
GS
Harley
John B
JB
James
Judith A
JA
Nath
Swapan K
SK
D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D053495:Osteopontin / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
D053495:Osteopontin