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2. Genome-wide association study for systemic lupus erythematosus in an egyptian population

Author

Elghzaly, Ashraf A, Sun, Celi, Looger, Loren L, Hirose, Misa, Salama, Mohamed, Khalil, Noha M, Behiry, Mervat Essam, Hegazy, Mohamed Tharwat, Hussein, Mohamed Ahmed, Salem, Mohamad Nabil, Eltoraby, Ehab, Tawhid, Ziyad, Alwasefy, Mona, Allam, Walaa, El-Shiekh, Iman, Elserafy, Menattallah, Abdelnaser, Anwar, Hashish, Sara, Shebl, Nourhan, Shahba, Abeer Abdelmonem, Elgirby, Amira, Hassab, Amina, Refay, Khalida, El-Touchy, Hanan Mohamed, Youssef, Ali, Shabacy, Fatma, Hashim, Abdelkader Ahmed, Abdelzaher, Asmaa, Alshebini, Emad, Fayez, Dalia, El-Bakry, Samah A, Elzohri, Mona H, Abdelsalam, Eman Nagiub, El-Khamisy, Sherif F, Ibrahim, Saleh, Ragab, Gaafar, and Nath, Swapan K

Subjects
Biological Sciences, Genetics, Prevention, Human Genome, Biotechnology, Autoimmune Disease, Lupus, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, GWAS, lupus, admixture, Egypt, imputation, Clinical Sciences, Law
Abstract

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Published
2022

3. Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis

Author

Singh, Bhupinder, Maiti, Guru P, Zhou, Xujie, Fazel-Najafabadi, Mehdi, Bae, Sang-Cheol, Sun, Celi, Terao, Chikashi, Okada, Yukinori, Heng Chua, Kek, Kochi, Yuta, Guthridge, Joel M, Zhang, Hong, Weirauch, Matthew, James, Judith A, Harley, John B, Varshney, Gaurav K, Looger, Loren L, and Nath, Swapan K

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Biotechnology, Genetics, Human Genome, Autoimmune Disease, Lupus, 1.1 Normal biological development and functioning, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, Generic health relevance, Inflammatory and immune system, Alleles, Apoptosis, Cell Proliferation, Computational Biology, Cyclin-Dependent Kinase Inhibitor p27, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lupus Erythematosus, Systemic, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveIn a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.MethodsWe performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.ResultsWe replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.ConclusionCollectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

Published
2021

7. 1401 A Genome Wide Association Scan of SLE genetic risk in a cohort of African-American persons

Author

Harley, Isaac TW, primary, Sun, Celi, additional, Williams, Adrienne H, additional, Ziegler, Julie T, additional, Comeau, Mary E, additional, Marion, Miranda C, additional, Glenn, Stuart B, additional, Adler, Adam, additional, Frank-Pearce, Summer G, additional, Shen, Nan, additional, Kelly, Jennifer A, additional, Namjou-Khales, Bahram, additional, Petri, Michelle, additional, Alarcon-Riquelme, Marta, additional, Joseph McCune, W, additional, Gaffney, Patrick, additional, Sivils, Kathy, additional, Salmon, Jane E, additional, Weisman, Michael H, additional, Edberg, Jeffrey C, additional, Brown, Elizabeth E, additional, Utset, Tammy, additional, Criswell, Lindsey A, additional, Jacob, Chaim O, additional, Tsao, Betty, additional, Vyse, Timothy J, additional, James, Judith A, additional, Gilkeson, Gary S, additional, Kamen, Diane L, additional, Montgomery, Courtney, additional, Merrill, Joan T, additional, Nath, Swapan K, additional, Laurynenka, Viktoryia, additional, Chepelev, Iouri, additional, Harris-Lewis, Valerie, additional, Hal Scofield, R, additional, Kimberly, Robert P, additional, Langefeld, Carl D, additional, Harley, John B, additional, and Kaufman, Kenneth M, additional

Published
2022
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8. Angiogenesis related genes in Takayasu Arteritis (TAK): robust association with Tag SNPs of IL-18and FGF-2in a South Asian Cohort

Author

Danda, Debashish, Goel, Ruchika, Kabeerdoss, Jayakanthan, Sun, Celi, Danda, Sumita, Lincy Franklin, Anisea, Joseph, George, and Nath, Swapan K.

Abstract

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18(encodes Interleukin-18), FGF2(encodes Fibroblast Growth Factor-2), and ANGPT1(encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p< 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18(rs187238 and rs1946518) and one 3’UTR tag SNP (rs1476217) of FGF2were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25–2.17), 0.03 and 1.28 (1.02–1.64) & 0.016 and 1.33 (1.05–1.67), respectively; while, the two tag SNPs of ANGPT1gene (rs6469101 and rs16875900) showed a trend (p= 0.055 & p= 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18and FGF2genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

Published
2024
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9. Genome-wide association study for systemic lupus erythematosus in an egyptian population

Author

Elghzaly, Ashraf A., primary, Sun, Celi, additional, Looger, Loren L., additional, Hirose, Misa, additional, Salama, Mohamed, additional, Khalil, Noha M., additional, Behiry, Mervat Essam, additional, Hegazy, Mohamed Tharwat, additional, Hussein, Mohamed Ahmed, additional, Salem, Mohamad Nabil, additional, Eltoraby, Ehab, additional, Tawhid, Ziyad, additional, Alwasefy, Mona, additional, Allam, Walaa, additional, El-Shiekh, Iman, additional, Elserafy, Menattallah, additional, Abdelnaser, Anwar, additional, Hashish, Sara, additional, Shebl, Nourhan, additional, Shahba, Abeer Abdelmonem, additional, Elgirby, Amira, additional, Hassab, Amina, additional, Refay, Khalida, additional, El-Touchy, Hanan Mohamed, additional, Youssef, Ali, additional, Shabacy, Fatma, additional, Hashim, Abdelkader Ahmed, additional, Abdelzaher, Asmaa, additional, Alshebini, Emad, additional, Fayez, Dalia, additional, El-Bakry, Samah A., additional, Elzohri, Mona H., additional, Abdelsalam, Eman Nagiub, additional, El-Khamisy, Sherif F., additional, Ibrahim, Saleh, additional, Ragab, Gaafar, additional, and Nath, Swapan K., additional

Published
2022
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11. Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci

Author

Molineros, Julio E., Yang, Wanling, Zhou, Xu-jie, Sun, Celi, Okada, Yukinori, Zhang, Huoru, Heng Chua, Kek, Lau, Yu-Lung, Kochi, Yuta, Suzuki, Akari, Yamamoto, Kazuhiko, Ma, Jianyang, Bang, So-Young, Lee, Hye-Soon, Kim, Kwangwoo, Bae, Sang-Cheol, Zhang, Hong, Shen, Nan, Looger, Loren L., and Nath, Swapan K.

Published
2017
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13. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility

Author

Molineros, Julio E., primary, Singh, Bhupinder, additional, Terao, Chikashi, additional, Okada, Yukinori, additional, Kaplan, Jakub, additional, McDaniel, Barbara, additional, Akizuki, Shuji, additional, Sun, Celi, additional, Webb, Carol F., additional, Looger, Loren L., additional, and Nath, Swapan K., additional

Published
2019
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14. Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians

Author

Molineros, Julio E., primary, Looger, Loren L., additional, Kim, Kwangwoo, additional, Okada, Yukinori, additional, Terao, Chikashi, additional, Sun, Celi, additional, Zhou, Xu-jie, additional, Raj, Prithvi, additional, Kochi, Yuta, additional, Suzuki, Akari, additional, Akizuki, Shuji, additional, Nakabo, Shuichiro, additional, Bang, So-Young, additional, Lee, Hye-Soon, additional, Kang, Young Mo, additional, Suh, Chang-Hee, additional, Chung, Won Tae, additional, Park, Yong-Beom, additional, Choe, Jung-Yoon, additional, Shim, Seung-Cheol, additional, Lee, Shin-Seok, additional, Zuo, Xiaoxia, additional, Yamamoto, Kazuhiko, additional, Li, Quan-Zhen, additional, Shen, Nan, additional, Porter, Lauren L., additional, Harley, John B., additional, Chua, Kek Heng, additional, Zhang, Hong, additional, Wakeland, Edward K., additional, Tsao, Betty P., additional, Bae, Sang-Cheol, additional, and Nath, Swapan K., additional

Published
2019
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15. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility

Author

50626637, Molineros, Julio E., Singh, Bhupinder, Terao, Chikashi, Okada, Yukinori, Kaplan, Jakub, McDaniel, Barbara, Akizuki, Shuji, Sun, Celi, Webb, Carol F., Looger, Loren L., Nath, Swapan K., 50626637, Molineros, Julio E., Singh, Bhupinder, Terao, Chikashi, Okada, Yukinori, Kaplan, Jakub, McDaniel, Barbara, Akizuki, Shuji, Sun, Celi, Webb, Carol F., Looger, Loren L., and Nath, Swapan K.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component. We recently identified a novel SLE susceptibility locus near RASGRP1, which governs the ERK/MAPK kinase cascade and B-/T-cell differentiation and development. However, precise causal RASGRP1 functional variant(s) and their mechanisms of action in SLE pathogenesis remain undefined. Our goal was to fine-map this locus, prioritize genetic variants likely to be functional, experimentally validate their biochemical mechanisms, and determine the contribution of these SNPs to SLE risk. We performed a meta-analysis across six Asian and European cohorts (9, 529 cases; 22, 462 controls), followed by in silico bioinformatic and epigenetic analyses to prioritize potentially functional SNPs. We experimentally validated the functional significance and mechanism of action of three SNPs in cultured T-cells. Meta-analysis identified 18 genome-wide significant (p < 5 × 10−8) SNPs, mostly concentrated in two haplotype blocks, one intronic and the other intergenic. Epigenetic fine-mapping, allelic, eQTL, and imbalance analyses predicted three transcriptional regulatory regions with four SNPs (rs7170151, rs11631591-rs7173565, and rs9920715) prioritized for functional validation. Luciferase reporter assays indicated significant allele-specific enhancer activity for intronic rs7170151 and rs11631591-rs7173565 in T-lymphoid (Jurkat) cells, but not in HEK293 cells. Following up with EMSA, mass spectrometry, and ChIP-qPCR, we detected allele-dependent interactions between heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and rs11631591. Furthermore, inhibition of hnRNP-K in Jurkat and primary T-cells downregulated RASGRP1 and ERK/MAPK signaling. Comprehensive association, bioinformatics, and epigenetic analyses yielded putative functional variants of RASGRP1, which were experimentally validated. Notably, intronic variant (rs11631591) is located in a cell type-specific enhancer sequence, where its r

Published
2019

16. Amino acid signatures of HLA Class-I and II molecules are strongly associated with SLE susceptibility and autoantibody production in Eastern Asians

Author

50626637, Molineros, Julio E., Looger, Loren L., Kim, Kwangwoo, Okada, Yukinori, Terao, Chikashi, Sun, Celi, Zhou, Xu-jie, Raj, Prithvi, Kochi, Yuta, Suzuki, Akari, Akizuki, Shuji, Nakabo, Shuichiro, Bang, So-Young, Lee, Hye-Soon, Kang, Young Mo, Suh, Chang-Hee, Chung, Won Tae, Park, Yong-Beom, Choe, Jung-Yoon, Shim, Seung-Cheol, Lee, Shin-Seok, Zuo, Xiaoxia, Yamamoto, Kazuhiko, Li, Quan-Zhen, Shen, Nan, Porter, Lauren L., Harley, John B., Chua, Kek Heng, Zhang, Hong, Wakeland, Edward K., Tsao, Betty P., Bae, Sang-Cheol, Nath, Swapan K., 50626637, Molineros, Julio E., Looger, Loren L., Kim, Kwangwoo, Okada, Yukinori, Terao, Chikashi, Sun, Celi, Zhou, Xu-jie, Raj, Prithvi, Kochi, Yuta, Suzuki, Akari, Akizuki, Shuji, Nakabo, Shuichiro, Bang, So-Young, Lee, Hye-Soon, Kang, Young Mo, Suh, Chang-Hee, Chung, Won Tae, Park, Yong-Beom, Choe, Jung-Yoon, Shim, Seung-Cheol, Lee, Shin-Seok, Zuo, Xiaoxia, Yamamoto, Kazuhiko, Li, Quan-Zhen, Shen, Nan, Porter, Lauren L., Harley, John B., Chua, Kek Heng, Zhang, Hong, Wakeland, Edward K., Tsao, Betty P., Bae, Sang-Cheol, and Nath, Swapan K.

Abstract

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4, 915 SLE cases and 13, 513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II

Published
2019

17. A Rare Variant (rs933717) atFBXO 31‐ MAP 1 LC 3Bin Chinese Is Associated With Systemic Lupus Erythematosus

Author

Qi, Yuan‐yuan, primary, Zhou, Xu‐jie, additional, Nath, Swapan K., additional, Sun, Celi, additional, Wang, Yan‐na, additional, Hou, Ping, additional, Mu, Rong, additional, Li, Chun, additional, Guo, Jian‐ping, additional, Li, Zhan‐guo, additional, Wang, Geng, additional, Xu, Hu‐ji, additional, Hao, Yan‐jie, additional, Zhang, Zhuo‐li, additional, Yue, Wei‐hua, additional, Zhang, Huoru, additional, Zhao, Ming‐hui, additional, and Zhang, Hong, additional

Published
2018
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19. Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy

Author

Zhou, Xu-Jie, primary, Nath, Swapan K, additional, Qi, Yuan-Yuan, additional, Sun, Celi, additional, Hou, Ping, additional, Zhang, Yue-Miao, additional, Lv, Ji-Cheng, additional, Shi, Su-Fang, additional, Liu, Li-Jun, additional, Chen, Ruoyan, additional, Yang, Wanling, additional, He, Kevin, additional, Li, Yanming, additional, and Zhang, Hong, additional

Published
2016
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20. High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry

Author

Sun, Celi, primary, Molineros, Julio E, additional, Looger, Loren L, additional, Zhou, Xu-jie, additional, Kim, Kwangwoo, additional, Okada, Yukinori, additional, Ma, Jianyang, additional, Qi, Yuan-yuan, additional, Kim-Howard, Xana, additional, Motghare, Prasenjeet, additional, Bhattarai, Krishna, additional, Adler, Adam, additional, Bang, So-Young, additional, Lee, Hye-Soon, additional, Kim, Tae-Hwan, additional, Kang, Young Mo, additional, Suh, Chang-Hee, additional, Chung, Won Tae, additional, Park, Yong-Beom, additional, Choe, Jung-Yoon, additional, Shim, Seung Cheol, additional, Kochi, Yuta, additional, Suzuki, Akari, additional, Kubo, Michiaki, additional, Sumida, Takayuki, additional, Yamamoto, Kazuhiko, additional, Lee, Shin-Seok, additional, Kim, Young Jin, additional, Han, Bok-Ghee, additional, Dozmorov, Mikhail, additional, Kaufman, Kenneth M, additional, Wren, Jonathan D, additional, Harley, John B, additional, Shen, Nan, additional, Chua, Kek Heng, additional, Zhang, Hong, additional, Bae, Sang-Cheol, additional, and Nath, Swapan K, additional

Published
2016
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22. A Rare Variant (rs933717) at <italic>FBXO31‐MAP1LC3B</italic> in Chinese Is Associated With Systemic Lupus Erythematosus.

Author

Qi, Yuan‐yuan, Zhou, Xu‐jie, Wang, Yan‐na, Hou, Ping, Hao, Yan‐jie, Zhang, Zhuo‐li, Zhao, Ming‐hui, Zhang, Hong, Nath, Swapan K., Sun, Celi, Mu, Rong, Li, Chun, Guo, Jian‐ping, Li, Zhan‐guo, Wang, Geng, Xu, Hu‐ji, Yue, Wei‐hua, and Zhang, Huoru

Subjects
AUTOPHAGY, ALLELES, BIOLOGICAL assay, CARRIER proteins, CELL lines, CHINESE people, GENE expression, GENETIC polymorphisms, GENETIC techniques, PROTEINS, SYSTEMIC lupus erythematosus, T cells, MICROARRAY technology, ODDS ratio
Abstract

Objective: Recent evidence from genetic, cell biology, and animal model studies has suggested a pivotal role of autophagy in mediating systemic lupus erythematosus (SLE). However, the genetic basis has not yet been thoroughly examined. Therefore, the aim of the present study was to identify additional susceptibility variants in autophagy‐related genes along with their functional significance. Methods: First, we performed a gene family–based genetic association analysis in SLE patients with the use of ImmunoChip arrays, and then we selected the most strongly associated polymorphisms for replication in additional cohorts. To identify regulatory clues, we analyzed publicly available blood expression quantitative trait locus data and Encyclopedia of DNA Elements data on transcription factor binding sites and cell type‐specific differential expression. Functional effects were tested by luciferase reporter assays, electrophoretic mobility shift assays, and differential gene expression assays. Results: In 14,474 samples, we observed that the rare Chinese variant rs933717T was associated with susceptibility to SLE (0.11% in cases versus 0.87% in controls; P = 2.36 × 10–10, odds ratio 0.13). The rs933717 risk allele C correlated with increased MAP1LC3B expression; increased MAP1LC3B messenger RNA was observed in SLE patients and in lupus‐prone mice. In reporter gene constructs, the risk allele increased luciferase activity up to 2.7‐3.8‐fold in both HEK 293T and Jurkat cell lines, and the binding of HEK 293T and Jurkat cell nuclear extracts to the risk allele was also increased. Conclusion: We observed a likely genetic association between light chain 3B, a widely used marker for autophagy, and susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Published
2018
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