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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-03-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001757&type=printable |
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| author | Shizhong Han Joel M Guthridge Isaac T W Harley Andrea L Sestak Xana Kim-Howard Kenneth M Kaufman Bahram Namjou Harshal Deshmukh Gail Bruner Luis R Espinoza Gary S Gilkeson John B Harley Judith A James Swapan K Nath |
| author_facet | Shizhong Han Joel M Guthridge Isaac T W Harley Andrea L Sestak Xana Kim-Howard Kenneth M Kaufman Bahram Namjou Harshal Deshmukh Gail Bruner Luis R Espinoza Gary S Gilkeson John B Harley Judith A James Swapan K Nath |
| author_sort | Shizhong Han |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e291051d6aea40bc92ed01d7fb7fa7bc |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e291051d6aea40bc92ed01d7fb7fa7bc2025-08-20T03:55:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-03-0133e000175710.1371/journal.pone.0001757Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction.Shizhong HanJoel M GuthridgeIsaac T W HarleyAndrea L SestakXana Kim-HowardKenneth M KaufmanBahram NamjouHarshal DeshmukhGail BrunerLuis R EspinozaGary S GilkesonJohn B HarleyJudith A JamesSwapan K NathOsteopontin (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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001757&type=printable |
| spellingShingle | Shizhong Han Joel M Guthridge Isaac T W Harley Andrea L Sestak Xana Kim-Howard Kenneth M Kaufman Bahram Namjou Harshal Deshmukh Gail Bruner Luis R Espinoza Gary S Gilkeson John B Harley Judith A James Swapan K Nath Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. PLoS ONE |
| title | Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. |
| title_full | Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. |
| title_fullStr | Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. |
| title_full_unstemmed | Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. |
| title_short | Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction. |
| title_sort | osteopontin and systemic lupus erythematosus association a probable gene gender interaction |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001757&type=printable |
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