Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

Wenfeng Tan, Katsue Sunahori, Jian Zhao, Yun Deng, Kenneth M. Kaufman, Jennifer A. Kelly, Carl D. Langefeld, Adrienne H. Williams, Mary E. Comeau, Julie T. Ziegler, Miranda C. Marion, Sang Cheol Bae, Joo Hyun Lee, Ji Seon Lee, Deh Ming Chang, Yeong Wook Song, Chack Yung Yu, Robert P. Kimberly, Jeffrey C. Edberg, Elizabeth E. BrownMichelle A. Petri, Rosalind Ramsey-Goldman, Luis M. Vilá, John D. Reveille, Marta E. Alarcõn-Riquelme, John B. Harley, Susan A. Boackle, Anne M. Stevens, R. Hal Scofield, Joan T. Merrill, Barry I. Freedman, Juan Manuel Anaya, Lindsey A. Criswell, Chaim O. Jacob, Timothy J. Vyse, Timothy B. Niewold, Patrick M. Gaffney, Kathy L. Moser, Gary S. Gilkeson, Diane L. Kamen, Judith A. James, Jennifer M. Grossman, Bevra H. Hahn, George C. Tsokos, Betty P. Tsao

Resultado de la investigación: Contribución a RevistaArtículo

24 Citas (Scopus)

Resumen

Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology.
Idioma originalEnglish (US)
Páginas (desde-hasta)2755-2763
Número de páginas9
PublicaciónArthritis and Rheumatism
DOI
EstadoPublished - sep 1 2011

Huella dactilar

Ethnic Groups
Systemic Lupus Erythematosus
Asian Americans
Hispanic Americans
Single Nucleotide Polymorphism
T-Lymphocytes
Interleukin-2
Genotype
African Americans
Introns
Haplotypes
Meta-Analysis
Real-Time Polymerase Chain Reaction
Anti-Idiotypic Antibodies
Alleles
Odds Ratio
Confidence Intervals
Kidney
DNA
Population

Citar esto

Tan, W., Sunahori, K., Zhao, J., Deng, Y., Kaufman, K. M., Kelly, J. A., ... Tsao, B. P. (2011). Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. Arthritis and Rheumatism, 2755-2763. https://doi.org/10.1002/art.30452
Tan, Wenfeng ; Sunahori, Katsue ; Zhao, Jian ; Deng, Yun ; Kaufman, Kenneth M. ; Kelly, Jennifer A. ; Langefeld, Carl D. ; Williams, Adrienne H. ; Comeau, Mary E. ; Ziegler, Julie T. ; Marion, Miranda C. ; Bae, Sang Cheol ; Lee, Joo Hyun ; Lee, Ji Seon ; Chang, Deh Ming ; Song, Yeong Wook ; Yu, Chack Yung ; Kimberly, Robert P. ; Edberg, Jeffrey C. ; Brown, Elizabeth E. ; Petri, Michelle A. ; Ramsey-Goldman, Rosalind ; Vilá, Luis M. ; Reveille, John D. ; Alarcõn-Riquelme, Marta E. ; Harley, John B. ; Boackle, Susan A. ; Stevens, Anne M. ; Scofield, R. Hal ; Merrill, Joan T. ; Freedman, Barry I. ; Anaya, Juan Manuel ; Criswell, Lindsey A. ; Jacob, Chaim O. ; Vyse, Timothy J. ; Niewold, Timothy B. ; Gaffney, Patrick M. ; Moser, Kathy L. ; Gilkeson, Gary S. ; Kamen, Diane L. ; James, Judith A. ; Grossman, Jennifer M. ; Hahn, Bevra H. ; Tsokos, George C. ; Tsao, Betty P. / Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. En: Arthritis and Rheumatism. 2011 ; pp. 2755-2763.
@article{00a02ba0278d41119d835720255930b5,
title = "Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups",
abstract = "Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95{\%} confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright {\circledC} 2011 by the American College of Rheumatology.",
author = "Wenfeng Tan and Katsue Sunahori and Jian Zhao and Yun Deng and Kaufman, {Kenneth M.} and Kelly, {Jennifer A.} and Langefeld, {Carl D.} and Williams, {Adrienne H.} and Comeau, {Mary E.} and Ziegler, {Julie T.} and Marion, {Miranda C.} and Bae, {Sang Cheol} and Lee, {Joo Hyun} and Lee, {Ji Seon} and Chang, {Deh Ming} and Song, {Yeong Wook} and Yu, {Chack Yung} and Kimberly, {Robert P.} and Edberg, {Jeffrey C.} and Brown, {Elizabeth E.} and Petri, {Michelle A.} and Rosalind Ramsey-Goldman and Vil{\'a}, {Luis M.} and Reveille, {John D.} and Alarc{\~o}n-Riquelme, {Marta E.} and Harley, {John B.} and Boackle, {Susan A.} and Stevens, {Anne M.} and Scofield, {R. Hal} and Merrill, {Joan T.} and Freedman, {Barry I.} and Anaya, {Juan Manuel} and Criswell, {Lindsey A.} and Jacob, {Chaim O.} and Vyse, {Timothy J.} and Niewold, {Timothy B.} and Gaffney, {Patrick M.} and Moser, {Kathy L.} and Gilkeson, {Gary S.} and Kamen, {Diane L.} and James, {Judith A.} and Grossman, {Jennifer M.} and Hahn, {Bevra H.} and Tsokos, {George C.} and Tsao, {Betty P.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1002/art.30452",
language = "English (US)",
pages = "2755--2763",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",

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Tan, W, Sunahori, K, Zhao, J, Deng, Y, Kaufman, KM, Kelly, JA, Langefeld, CD, Williams, AH, Comeau, ME, Ziegler, JT, Marion, MC, Bae, SC, Lee, JH, Lee, JS, Chang, DM, Song, YW, Yu, CY, Kimberly, RP, Edberg, JC, Brown, EE, Petri, MA, Ramsey-Goldman, R, Vilá, LM, Reveille, JD, Alarcõn-Riquelme, ME, Harley, JB, Boackle, SA, Stevens, AM, Scofield, RH, Merrill, JT, Freedman, BI, Anaya, JM, Criswell, LA, Jacob, CO, Vyse, TJ, Niewold, TB, Gaffney, PM, Moser, KL, Gilkeson, GS, Kamen, DL, James, JA, Grossman, JM, Hahn, BH, Tsokos, GC & Tsao, BP 2011, 'Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups', Arthritis and Rheumatism, pp. 2755-2763. https://doi.org/10.1002/art.30452

Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups. / Tan, Wenfeng; Sunahori, Katsue; Zhao, Jian; Deng, Yun; Kaufman, Kenneth M.; Kelly, Jennifer A.; Langefeld, Carl D.; Williams, Adrienne H.; Comeau, Mary E.; Ziegler, Julie T.; Marion, Miranda C.; Bae, Sang Cheol; Lee, Joo Hyun; Lee, Ji Seon; Chang, Deh Ming; Song, Yeong Wook; Yu, Chack Yung; Kimberly, Robert P.; Edberg, Jeffrey C.; Brown, Elizabeth E.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Vilá, Luis M.; Reveille, John D.; Alarcõn-Riquelme, Marta E.; Harley, John B.; Boackle, Susan A.; Stevens, Anne M.; Scofield, R. Hal; Merrill, Joan T.; Freedman, Barry I.; Anaya, Juan Manuel; Criswell, Lindsey A.; Jacob, Chaim O.; Vyse, Timothy J.; Niewold, Timothy B.; Gaffney, Patrick M.; Moser, Kathy L.; Gilkeson, Gary S.; Kamen, Diane L.; James, Judith A.; Grossman, Jennifer M.; Hahn, Bevra H.; Tsokos, George C.; Tsao, Betty P.

En: Arthritis and Rheumatism, 01.09.2011, p. 2755-2763.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

AU - Tan, Wenfeng

AU - Sunahori, Katsue

AU - Zhao, Jian

AU - Deng, Yun

AU - Kaufman, Kenneth M.

AU - Kelly, Jennifer A.

AU - Langefeld, Carl D.

AU - Williams, Adrienne H.

AU - Comeau, Mary E.

AU - Ziegler, Julie T.

AU - Marion, Miranda C.

AU - Bae, Sang Cheol

AU - Lee, Joo Hyun

AU - Lee, Ji Seon

AU - Chang, Deh Ming

AU - Song, Yeong Wook

AU - Yu, Chack Yung

AU - Kimberly, Robert P.

AU - Edberg, Jeffrey C.

AU - Brown, Elizabeth E.

AU - Petri, Michelle A.

AU - Ramsey-Goldman, Rosalind

AU - Vilá, Luis M.

AU - Reveille, John D.

AU - Alarcõn-Riquelme, Marta E.

AU - Harley, John B.

AU - Boackle, Susan A.

AU - Stevens, Anne M.

AU - Scofield, R. Hal

AU - Merrill, Joan T.

AU - Freedman, Barry I.

AU - Anaya, Juan Manuel

AU - Criswell, Lindsey A.

AU - Jacob, Chaim O.

AU - Vyse, Timothy J.

AU - Niewold, Timothy B.

AU - Gaffney, Patrick M.

AU - Moser, Kathy L.

AU - Gilkeson, Gary S.

AU - Kamen, Diane L.

AU - James, Judith A.

AU - Grossman, Jennifer M.

AU - Hahn, Bevra H.

AU - Tsokos, George C.

AU - Tsao, Betty P.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology.

AB - Objective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ∼2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology.

U2 - 10.1002/art.30452

DO - 10.1002/art.30452

M3 - Article

C2 - 21590681

SP - 2755

EP - 2763

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

ER -