End-stage renal disease in African Americans with lupus nephritis is associated with APOL1.
End-stage renal disease in African Americans with lupus nephritis is associated with APOL1.
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患有狼疮性肾炎的非裔美国人的终末期肾病与 APOL1 相关。
DOI：
10.1002/art.38220
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发表时间：
2014-02
影响因子：
13.3
通讯作者：
Kimberly, Robert P.
中科院分区：
文献类型：
--
作者：
Freedman, Barry I.;Langefeld, Carl D.;Andringa, Kelly K.;Croker, Jennifer A.;Williams, Adrienne H.;Garner, Neva E.;Birmingham, Daniel J.;Hebert, Lee A.;Hicks, Pamela J.;Segal, Mark S.;Edberg, Jeffrey C.;Brown, Elizabeth E.;Alarcon, Graciela S.;Costenbader, Karen H.;Comeau, Mary E.;Criswell, Lindsey A.;Harley, John B.;James, Judith A.;Kamen, Diane L.;Lim, S. Sam;Merrill, Joan T.;Sivils, Kathy L.;Niewold, Timothy B.;Patel, Neha M.;Petri, Michelle;Ramsey-Goldman, Rosalind;Reveille, John D.;Salmon, Jane E.;Tsao, Betty P.;Gibson, Keisha L.;Byers, Joyce R.;Vinnikova, Anna K.;Lea, Janice P.;Julian, Bruce A.;Kimberly, Robert P.
狼疮性肾炎 (LN) 是系统性红斑狼疮 (SLE) 的严重表现，具有家族聚集性，并可能进展为终末期肾病 (ESRD)。 LN 在非裔美国人中比在欧洲裔美国人中更为普遍。本研究旨在调查载脂蛋白 L1 基因 (APOL1) 肾病风险等位基因 G1/G2（在非裔美国人中常见，在欧洲裔美国人中罕见）导致种族风险差异的假设。对 855 名患有 LN-ESRD 的非裔美国人 SLE 患者（病例）和 534 名无肾病的非裔美国人 SLE 患者（对照）进行 APOL1 G1 和 G2 肾病等位基因基因分型，并通过逻辑回归在隐性遗传模型下测试关联性。百分之九十的系统性红斑狼疮患者是女性。 LN-ESRD 病例诊断 SLE 时的平均±SD 年龄显着低于 SLE 非肾病对照（27.3 ± 10.9 岁 vs 39.5 ± 12.2 岁）。病例中从 SLE 诊断到发展为 LN-ESRD 的平均±SD时间为 7.3±7.2 年。 G1/G2 风险等位基因与 SLE-ESRD 密切相关，25% 的病例和 12% 的对照有 2 个肾病等位基因（比值比 [OR] 2.57，隐性模型 P = 1.49 × 10−9），并且在调整年龄、性别和血统混合后（OR 2.72，P = 6.23 × 10−6）。经年龄、性别和混合调整后，具有 G1/G2 多态性的患者中 ESRD 的人群归因风险为 0.26，而欧洲裔美国患者中该风险为 0.003。具有 APOL1 风险基因型的个体从 SLE 诊断到 ESRD 发展的平均时间提前了约 2 年 (P = 0.01)。 APOL1 G1/G2 等位基因强烈影响非裔美国人患 LN-ESRD 的风险以及进展为 ESRD 的时间。这些等位基因在非裔美国人中出现频率较高，而在欧洲裔美国人中几乎不存在，这解释了非裔美国人 LN-ESRD 风险增加的重要原因。
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk. APOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression. Ninety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10−9), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10−6). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ~2 years earlier among individuals with APOL1 risk genotypes (P = 0.01). APOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
--
作者：
Petri, Michelle;Orbai, Ana-Maria;Alarcon, Graciela S.;Gordon, Caroline;Merrill, Joan T.;Fortin, Paul R.;Bruce, Ian N.;Isenberg, David;Wallace, Daniel J.;Nived, Ola;Sturfelt, Gunnar;Ramsey-Goldman, Rosalind;Bae, Sang-Cheol;Hanly, John G.;Sanchez-Guerrero, Jorge;Clarke, Ann;Aranow, Cynthia;Manzi, Susan;Urowitz, Murray;Gladman, Dafna;Kalunian, Kenneth;Costner, Melissa;Werth, Victoria P.;Zoma, Asad;Bernatsky, Sasha;Ruiz-Irastorza, Guillermo;Khamashta, Munther A.;Jacobsen, Soren;Buyon, Jill P.;Maddison, Peter;Dooley, Mary Anne;van vollenhoven, Ronald F.;Ginzler, Ellen;Stoll, Thomas;Peschken, Christine;Jorizzo, Joseph L.;Callen, Jeffrey P.;Lim, S. Sam;Fessler, Barri J.;Inanc, Murat;Kamen, Diane L.;Rahman, Anisur;Steinsson, Kristjan;Franks, Andrew G., Jr.;Sigler, Lisa;Hameed, Suhail;Fang, Hong;Ngoc Pham;Brey, Robin;Weisman, Michael H.;McGwin, Gerald, Jr.;Magder, Laurence S.
通讯作者：
Magder, Laurence S.
影响因子：
3.3
作者：
Ramos, Paula S.;Brown, Elisabeth E.;Kimberly, Robert P.;Langefeld, Carl D.
通讯作者：
Langefeld, Carl D.
影响因子：
5
作者：
通讯作者：
--
影响因子：
13.6
作者：
Kopp, Jeffrey B.;Nelson, George W.;Winkler, Cheryl A.
通讯作者：
Winkler, Cheryl A.