Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients.
Early disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients.
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DOI：
10.1136/ard.2010.141697
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发表时间：
2011-01
影响因子：
27.4
通讯作者：
Sawalha AH
中科院分区：
文献类型：
--
作者：
Webb R;Kelly JA;Somers EC;Hughes T;Kaufman KM;Sanchez E;Nath SK;Bruner G;Alarcón-Riquelme ME;Gilkeson GS;Kamen DL;Richardson BC;Harley JB;Sawalha AH
系统性红斑狼疮（SLE）是一种慢性、多器官、自身免疫性疾病，影响所有年龄和种族的人。探讨SLE发病年龄与多种临床表现之间的关系。此外，确定SLE患者发病年龄与遗传风险之间的关系。在一个1317例多种族患者队列中探讨了发病年龄与SLE表现之间的关系。SLE患者在19个已证实的SLE遗传易感性位点进行基因分型。采用Logistic回归分析确定危险等位基因的数量与发病年龄之间的关系。儿童期SLE发生蛋白尿、颧骨皮疹、抗dsDNA抗体、溶血性贫血、关节炎和白细胞减少的几率较高（OR分别为3.03、2.13、2.08、2.50、1.89、1.53; p值分别<0.0001、0.0004、0.0005、0.0024、0.0114、0.045）。在女性受试者中，儿童期发病的SLE出现细胞管型的几率是成人期发病的SLE的2.18倍（p=0.0027）。发病年龄≥50岁，出现蛋白尿、细胞管型、抗nRNP抗体、抗Sm抗体、抗dsDNA抗体和癫痫发作的几率降低。然而，晚期成人型SLE患者比早期成人型患者发生光敏性的几率更高。SLE患者基因组中携带的每个SLE易感性风险等位基因以种族特异性方式增加了儿童期发病疾病的几率：在Gullah中平均为48%，在非洲裔美国人中为25%，但这在西班牙裔和欧洲裔美国人狼疮患者中并不显著。首次量化了遗传对预测SLE患者早发性疾病的贡献。在一个大型多种族队列中，在早发性疾病患者中发现了更严重的SLE表型，与性别、种族和疾病持续时间无关。
Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities. To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE. The relationship between the age at disease onset and SLE manifestations were explored in a multiracial cohort of 1317 patients. Patients with SLE were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset. Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values <0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in adult-onset SLE (p=0.0027). With age of onset ≥50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody and seizures were reduced. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specific manner: by an average of 48% in Gullah and 25% in African-Americans, but this was not significant in Hispanic and European-American lupus patients. The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.
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影响因子：
2.6
作者：
Zonana-Nacach, A;Camargo-Coronel, A;Fraga, A
通讯作者：
Fraga, A
影响因子：
--
作者：
Brunner, Hermine I.;Gladman, Dafna D.;Silverman, Earl D.
通讯作者：
Silverman, Earl D.
影响因子：
--
作者：
Scofield, R. Hal;Bruner, Gail R.;Namjou, Bahram;Kimberly, Robert P.;Ramsey-Goldman, Rosalind;Petri, Michelle;Reveille, John D.;Alarcon, Graciela S.;Vila, Luis A.;Reid, Jeff;Harris, Bryan;Li, Shibo;Kelly, Jennifer A.;Harley, John B.
通讯作者：
Harley, John B.
影响因子：
--
作者：
Alarcon-Segovia, D;Alarcón-Riquelme, ME;Pons-Estel, BA
通讯作者：
Pons-Estel, BA
影响因子：
3.9
作者：
Hiraki, Linda T.;Benseler, Susanne M.;Silverman, Earl D.
通讯作者：
Silverman, Earl D.