Genetic Variants of IκB Kinase β (IKBKB) and Polymerase β (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population

PLOS ONE, Dec 2019

A previous large-scale replication study validation of a genome wide association study (GWAS) identified IκB kinase β (IKBKB) single nucleotide polymorphisms (SNPs) as a risk factor associated with systemic lupus erythematosus (SLE) in a Chinese Han population. IKBKB SNPs were associated with polymerase β (POLB) SNPs and reduced POLB expression, and this was proposed to be an underlying cause of human SLE development. In the current case-control study, we evaluated IKBKB (rs12676482 and rs2272733) and POLB (rs3136717 and rs3136744) SNPs in 946 SLE patients and 961 healthy controls. We investigated the possible association of these four SNPs with SLE in a Chinese Han population using the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The differences in the frequencies of the four SNP alleles and the genotypes and haplotypes of the POLB polymorphisms were statistically insignificant when the SLE patients were compared with the controls in the Chinese Han population enrolled in this study (all, p ˃ 0.05). Furthermore, no associations were detected using different genetic models (additive, dominant, and recessive; all, p ˃ 0.05). Our findings indicate that the IKBKB (rs12676482 and rs2272733) and POLB (rs3136717, rs3136744) SNPs confer no genetic predisposition to SLE risk in this Chinese Han population.

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Genetic Variants of IκB Kinase β (IKBKB) and Polymerase β (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population

July Genetic Variants of IκB Kinase β (IKBKB) and Polymerase β (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population Yuan Li 0 1 Ziyan Wu 0 1 Shulan Zhang 0 1 Si Chen 0 1 Ping Li 0 1 Jing Li 0 1 Chongwei Cao 0 1 Bin Liu 0 1 Fengchun Zhang 0 1 Yongzhe Li 0 1 0 1 Department of Rheumatology, the Affiliated Hospital of Qingdao University , Qingdao , China , 2 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China 1 Editor: Graham R. Wallace, University of Birmingham , UNITED KINGDOM A previous large-scale replication study validation of a genome wide association study (GWAS) identified IκB kinase β (IKBKB) single nucleotide polymorphisms (SNPs) as a risk factor associated with systemic lupus erythematosus (SLE) in a Chinese Han population. IKBKB SNPs were associated with polymerase β (POLB) SNPs and reduced POLB expression, and this was proposed to be an underlying cause of human SLE development. In the current case-control study, we evaluated IKBKB (rs12676482 and rs2272733) and POLB (rs3136717 and rs3136744) SNPs in 946 SLE patients and 961 healthy controls. We investigated the possible association of these four SNPs with SLE in a Chinese Han population using the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The differences in the frequencies of the four SNP alleles and the genotypes and haplotypes of the POLB polymorphisms were statistically insignificant when the SLE patients were compared with the controls in the Chinese Han population enrolled in this study (all, p > 0.05). Furthermore, no associations were detected using different genetic models (additive, dominant, and recessive; all, p > 0.05). Our findings indicate that the IKBKB (rs12676482 and rs2272733) and POLB (rs3136717, rs3136744) SNPs confer no genetic predisposition to SLE risk in this Chinese Han population. - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by funding from the Research Special Fund for Public Welfare Industry of Health No. 201202004 (to FCZ), and the National Natural Science Foundation of China Grants 81072486, 81172857, 81373188 (to YZL) and the Natural Sciences Foundation of China No.81241094 (to BL) and Technology program of basic research projects of Qingdao city No.13-1-4-138-jch (BL). Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that causes the immune system to attack healthy tissues and organs through the production of a diverse array of autoantibodies, complement activation and immune complex formation [1]. SLE prevalence ranges from 0.031% to 0.07% in China and from 0.007% to 0.071% in Europe [2,3]. SLE affects Competing Interests: The authors have declared that no competing interests exist. more women than men (a ratio of 9:1, female to male), especially during the childbearing years [4]. Although the etiology and pathogenesis of SLE remain unknown, it is possible that environmental and epigenetic factors contribute to SLE [5]. SLE frequently develops in people with a family history of the disease, and a number of likely candidate genes have been investigated. For instance, the HLA class I, II and III genes have been associated with SLE development [6]. Additionally, the X chromosome carries immunological related genes, and, thus, it is possible that X chromosome mutations could contribute to SLE onset. However, no single causal gene has yet been conclusively identified. Thus, further investigation of SLE genetic susceptibility could provide a better understanding of SLE pathogenesis and help identify novel strategies for effective control of this chronic autoimmune disease. IκB kinase β (IKBKB) encodes IKK-β protein, a cytokine-activated intracellular immune response signaling component that acts via activation of the canonical NF-κB signaling pathway. The rs12676482 SNP was recently localized in IKBKB, and identified and significantly associated with SLE in a large-scale replication study based on a genome wide association study (GWAS) of a Chinese Han population [7]. Notably, rs12676482 is in perfect linkage disequilibrium with rs2272733 (r2 = 1), which is highly associated with decreased POLB expression [8]. Environmental factors may induce DNA damage, and this damage is normally recognized and repaired by complex mechanisms in cells [9,10]. However, recent studies have reported that DNA repair pathway genes may not work properly in SLE patients [11,12]. Therefore, DNA damage may induce the immune system to attack and induce the apoptosis of the affected cells and tissues. Indeed, SNPs in DNA repair genes have been associated with a predisposition to develop the autoantibodies and clinical manifestations of SLE [13,14] (...truncated)


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Yuan Li, Ziyan Wu, Shulan Zhang, Si Chen, Ping Li, Jing Li, Chongwei Cao, Bin Liu, Fengchun Zhang, Yongzhe Li. Genetic Variants of IκB Kinase β (IKBKB) and Polymerase β (POLB) Were Not Associated with Systemic Lupus Erythematosus Risk in a Chinese Han Population, PLOS ONE, 2015, 7, DOI: 10.1371/journal.pone.0132556