Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

Jian Zhao, Hui Wu, Melanie Khosravi, Huijuan Cui, Xiaoxia Qian, Jennifer A. Kelly, Kenneth M. Kaufman, Carl D. Langefeld, Adrienne H. Williams, Mary E. Comeau, Julie T. Ziegler, Miranda C. Marion, Adam Adler, Stuart B. Glenn, Marta E. Alarcón-Riquelme, [Unknown] BIOLUPUS Network, [Unknown] GENLES Network, Bernardo A. Pons-Estel, John B. Harley, Sang Cheol Bae & 37 otros So Young Bang, Soo Kyung Cho, Chaim O. Jacob, Timothy J. Vyse, Timothy B. Niewold, Patrick M. Gaffney, Kathy L. Moser, Robert P. Kimberly, Jeffrey C. Edberg, Elizabeth E. Brown, Graciela S. Alarcon, Michelle A. Petri, Rosalind Ramsey-Goldman, Luis M. Vilá, John D. Reveille, Judith A. James, Gary S. Gilkeson, Diane L. Kamen, Barry I. Freedman, Juan Manuel Anaya, Joan T. Merrill, Lindsey A. Criswell, R. Hal Scofield, Anne M. Stevens, Joel M. Guthridge, Deh Ming Chang, Yeong Wook Song, Ji Ah Park, Eun Young Lee, Susan A. Boackle, Jennifer M. Grossman, Bevra H. Hahn, Timothy H J Goodship, Rita M. Cantor, Chack Yung Yu, Nan Shen, Betty P. Tsao

Resultado de la investigación: Contribución a RevistaArtículo

113 Citas (Scopus)

Resumen

Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.
Idioma originalEnglish (US)
PublicaciónPLoS Genetics
DOI
EstadoPublished - may 1 2011

Huella dactilar

Complement Factor H
lupus erythematosus
African American
Systemic Lupus Erythematosus
complement
gene
Single Nucleotide Polymorphism
Genes
African Americans
genes
Asian Americans
ethnic group
Complement Activation
chromosome
amplification
Introns
probe
introns
protein
autoimmune diseases

Citar esto

Zhao, Jian ; Wu, Hui ; Khosravi, Melanie ; Cui, Huijuan ; Qian, Xiaoxia ; Kelly, Jennifer A. ; Kaufman, Kenneth M. ; Langefeld, Carl D. ; Williams, Adrienne H. ; Comeau, Mary E. ; Ziegler, Julie T. ; Marion, Miranda C. ; Adler, Adam ; Glenn, Stuart B. ; Alarcón-Riquelme, Marta E. ; BIOLUPUS Network, [Unknown] ; GENLES Network, [Unknown] ; Pons-Estel, Bernardo A. ; Harley, John B. ; Bae, Sang Cheol ; Bang, So Young ; Cho, Soo Kyung ; Jacob, Chaim O. ; Vyse, Timothy J. ; Niewold, Timothy B. ; Gaffney, Patrick M. ; Moser, Kathy L. ; Kimberly, Robert P. ; Edberg, Jeffrey C. ; Brown, Elizabeth E. ; Alarcon, Graciela S. ; Petri, Michelle A. ; Ramsey-Goldman, Rosalind ; Vilá, Luis M. ; Reveille, John D. ; James, Judith A. ; Gilkeson, Gary S. ; Kamen, Diane L. ; Freedman, Barry I. ; Anaya, Juan Manuel ; Merrill, Joan T. ; Criswell, Lindsey A. ; Scofield, R. Hal ; Stevens, Anne M. ; Guthridge, Joel M. ; Chang, Deh Ming ; Song, Yeong Wook ; Park, Ji Ah ; Lee, Eun Young ; Boackle, Susan A. ; Grossman, Jennifer M. ; Hahn, Bevra H. ; Goodship, Timothy H J ; Cantor, Rita M. ; Yu, Chack Yung ; Shen, Nan ; Tsao, Betty P. / Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. En: PLoS Genetics. 2011.
@article{922f1b3f621240a689bd39726079d650,
title = "Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility",
abstract = "Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.",
author = "Jian Zhao and Hui Wu and Melanie Khosravi and Huijuan Cui and Xiaoxia Qian and Kelly, {Jennifer A.} and Kaufman, {Kenneth M.} and Langefeld, {Carl D.} and Williams, {Adrienne H.} and Comeau, {Mary E.} and Ziegler, {Julie T.} and Marion, {Miranda C.} and Adam Adler and Glenn, {Stuart B.} and Alarc{\'o}n-Riquelme, {Marta E.} and {BIOLUPUS Network}, [Unknown] and {GENLES Network}, [Unknown] and Pons-Estel, {Bernardo A.} and Harley, {John B.} and Bae, {Sang Cheol} and Bang, {So Young} and Cho, {Soo Kyung} and Jacob, {Chaim O.} and Vyse, {Timothy J.} and Niewold, {Timothy B.} and Gaffney, {Patrick M.} and Moser, {Kathy L.} and Kimberly, {Robert P.} and Edberg, {Jeffrey C.} and Brown, {Elizabeth E.} and Alarcon, {Graciela S.} and Petri, {Michelle A.} and Rosalind Ramsey-Goldman and Vil{\'a}, {Luis M.} and Reveille, {John D.} and James, {Judith A.} and Gilkeson, {Gary S.} and Kamen, {Diane L.} and Freedman, {Barry I.} and Anaya, {Juan Manuel} and Merrill, {Joan T.} and Criswell, {Lindsey A.} and Scofield, {R. Hal} and Stevens, {Anne M.} and Guthridge, {Joel M.} and Chang, {Deh Ming} and Song, {Yeong Wook} and Park, {Ji Ah} and Lee, {Eun Young} and Boackle, {Susan A.} and Grossman, {Jennifer M.} and Hahn, {Bevra H.} and Goodship, {Timothy H J} and Cantor, {Rita M.} and Yu, {Chack Yung} and Nan Shen and Tsao, {Betty P.}",
year = "2011",
month = "5",
day = "1",
doi = "10.1371/journal.pgen.1002079",
language = "English (US)",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",

}

Zhao, J, Wu, H, Khosravi, M, Cui, H, Qian, X, Kelly, JA, Kaufman, KM, Langefeld, CD, Williams, AH, Comeau, ME, Ziegler, JT, Marion, MC, Adler, A, Glenn, SB, Alarcón-Riquelme, ME, BIOLUPUS Network, U, GENLES Network, U, Pons-Estel, BA, Harley, JB, Bae, SC, Bang, SY, Cho, SK, Jacob, CO, Vyse, TJ, Niewold, TB, Gaffney, PM, Moser, KL, Kimberly, RP, Edberg, JC, Brown, EE, Alarcon, GS, Petri, MA, Ramsey-Goldman, R, Vilá, LM, Reveille, JD, James, JA, Gilkeson, GS, Kamen, DL, Freedman, BI, Anaya, JM, Merrill, JT, Criswell, LA, Scofield, RH, Stevens, AM, Guthridge, JM, Chang, DM, Song, YW, Park, JA, Lee, EY, Boackle, SA, Grossman, JM, Hahn, BH, Goodship, THJ, Cantor, RM, Yu, CY, Shen, N & Tsao, BP 2011, 'Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility', PLoS Genetics. https://doi.org/10.1371/journal.pgen.1002079

Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. / Zhao, Jian; Wu, Hui; Khosravi, Melanie; Cui, Huijuan; Qian, Xiaoxia; Kelly, Jennifer A.; Kaufman, Kenneth M.; Langefeld, Carl D.; Williams, Adrienne H.; Comeau, Mary E.; Ziegler, Julie T.; Marion, Miranda C.; Adler, Adam; Glenn, Stuart B.; Alarcón-Riquelme, Marta E.; BIOLUPUS Network, [Unknown]; GENLES Network, [Unknown]; Pons-Estel, Bernardo A.; Harley, John B.; Bae, Sang Cheol; Bang, So Young; Cho, Soo Kyung; Jacob, Chaim O.; Vyse, Timothy J.; Niewold, Timothy B.; Gaffney, Patrick M.; Moser, Kathy L.; Kimberly, Robert P.; Edberg, Jeffrey C.; Brown, Elizabeth E.; Alarcon, Graciela S.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Vilá, Luis M.; Reveille, John D.; James, Judith A.; Gilkeson, Gary S.; Kamen, Diane L.; Freedman, Barry I.; Anaya, Juan Manuel; Merrill, Joan T.; Criswell, Lindsey A.; Scofield, R. Hal; Stevens, Anne M.; Guthridge, Joel M.; Chang, Deh Ming; Song, Yeong Wook; Park, Ji Ah; Lee, Eun Young; Boackle, Susan A.; Grossman, Jennifer M.; Hahn, Bevra H.; Goodship, Timothy H J; Cantor, Rita M.; Yu, Chack Yung; Shen, Nan; Tsao, Betty P.

En: PLoS Genetics, 01.05.2011.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility

AU - Zhao, Jian

AU - Wu, Hui

AU - Khosravi, Melanie

AU - Cui, Huijuan

AU - Qian, Xiaoxia

AU - Kelly, Jennifer A.

AU - Kaufman, Kenneth M.

AU - Langefeld, Carl D.

AU - Williams, Adrienne H.

AU - Comeau, Mary E.

AU - Ziegler, Julie T.

AU - Marion, Miranda C.

AU - Adler, Adam

AU - Glenn, Stuart B.

AU - Alarcón-Riquelme, Marta E.

AU - BIOLUPUS Network, [Unknown]

AU - GENLES Network, [Unknown]

AU - Pons-Estel, Bernardo A.

AU - Harley, John B.

AU - Bae, Sang Cheol

AU - Bang, So Young

AU - Cho, Soo Kyung

AU - Jacob, Chaim O.

AU - Vyse, Timothy J.

AU - Niewold, Timothy B.

AU - Gaffney, Patrick M.

AU - Moser, Kathy L.

AU - Kimberly, Robert P.

AU - Edberg, Jeffrey C.

AU - Brown, Elizabeth E.

AU - Alarcon, Graciela S.

AU - Petri, Michelle A.

AU - Ramsey-Goldman, Rosalind

AU - Vilá, Luis M.

AU - Reveille, John D.

AU - James, Judith A.

AU - Gilkeson, Gary S.

AU - Kamen, Diane L.

AU - Freedman, Barry I.

AU - Anaya, Juan Manuel

AU - Merrill, Joan T.

AU - Criswell, Lindsey A.

AU - Scofield, R. Hal

AU - Stevens, Anne M.

AU - Guthridge, Joel M.

AU - Chang, Deh Ming

AU - Song, Yeong Wook

AU - Park, Ji Ah

AU - Lee, Eun Young

AU - Boackle, Susan A.

AU - Grossman, Jennifer M.

AU - Hahn, Bevra H.

AU - Goodship, Timothy H J

AU - Cantor, Rita M.

AU - Yu, Chack Yung

AU - Shen, Nan

AU - Tsao, Betty P.

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.

AB - Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.

U2 - 10.1371/journal.pgen.1002079

DO - 10.1371/journal.pgen.1002079

M3 - Article

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

ER -