Limits...
Polymorphism rs3828903 within MICB Is Associated with Susceptibility to Systemic Lupus Erythematosus in a Northern Han Chinese Population.

Zhang YM, Zhou XJ, Cheng FJ, Qi YY, Hou P, Zhao MH, Zhang H - J Immunol Res (2016)

Bottom Line: In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)).Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing 100034, China.

ABSTRACT
Objectives. The variant rs3828903 within MICB, a nonclassical MHC class I chain-related gene, was detected to contribute to systemic lupus erythematosus (SLE) in a Caucasian population. This study aimed to investigate the association in a northern Han Chinese population. Methods. We recruited 1077 SLE patients and 793 controls for analysis. rs3828903 was genotyped by TaqMan allele discrimination assay. Using the public databases, its functional annotations and gene differential expression analysis of MICB were evaluated. Results. Significant association between the allele G of rs3828903 and risk susceptibility to SLE was observed after adjusting for sex and age (P = 1.87 × 10(-2)). In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)). Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls. Conclusion. An association between rs3828903 and susceptibility to SLE has been detected in a Chinese population. This together with the functional annotations of rs3828903 converts MICB into a main candidate in the pathogenesis of SLE.

No MeSH data available.


Related in: MedlinePlus

Systemic lupus erythematosus-associated rs3828903 predicted to be part of the motifs for Zfp740 and Zic_2 in both HaploReg v4.1 and RegulomeDB databases. (a, b) Degeneracy within the 16- and 9-base motifs is illustrated at all positions by the stacked letters at each position. The relative height of each letter is proportional to its overenrichment in the motif. A line is boxed around rs3828903-G; this systemic lupus erythematosus-associated risk allele G is predicted to form the 8th and the second nucleotide in the motifs. (c) Altering the rs3828903 allele from rs3828903-G to rs3828903-A decreases the binding affinity for transcription factors CACD_2, Irf_disc4, Zfp740, and Zic_2 in HaploReg v4.1 database.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4940546&req=5

fig1: Systemic lupus erythematosus-associated rs3828903 predicted to be part of the motifs for Zfp740 and Zic_2 in both HaploReg v4.1 and RegulomeDB databases. (a, b) Degeneracy within the 16- and 9-base motifs is illustrated at all positions by the stacked letters at each position. The relative height of each letter is proportional to its overenrichment in the motif. A line is boxed around rs3828903-G; this systemic lupus erythematosus-associated risk allele G is predicted to form the 8th and the second nucleotide in the motifs. (c) Altering the rs3828903 allele from rs3828903-G to rs3828903-A decreases the binding affinity for transcription factors CACD_2, Irf_disc4, Zfp740, and Zic_2 in HaploReg v4.1 database.

Mentions: In HaploReg v4.1 database, rs3828903 was predicted to locate in promoter histone marks, enhancer histone marks, DNase, proteins bound, and motifs changed regions within MICB. Four binding site motifs span the rs3828903 region for binding by the transcription factors (TFs) CACD_2, Irf_disc4, Zfp740, and Zic_2. The differences between the LOD scores for the alleles A and G (reference) were −3.8, −1.9, −6.4, and −2.8 for CACD_2, Irf_disc4, Zfp740, and Zic_2, respectively (Figure 1). Therefore, this model predicted a higher affinity to TFs for allele G (risk) relative to allele A. Also, in RegulomeDB database, rs3828903 showed a high score (1f, eQTL + TF binding/DNase peak). Consistent with the HaploReg v4.1 database, the motifs for binding by the TFs Zfp740 and Zic_2 have also been observed in RegulomeDB database (Figure 1), suggesting its potential role for gene expression regulation.


Polymorphism rs3828903 within MICB Is Associated with Susceptibility to Systemic Lupus Erythematosus in a Northern Han Chinese Population.

Zhang YM, Zhou XJ, Cheng FJ, Qi YY, Hou P, Zhao MH, Zhang H - J Immunol Res (2016)

Systemic lupus erythematosus-associated rs3828903 predicted to be part of the motifs for Zfp740 and Zic_2 in both HaploReg v4.1 and RegulomeDB databases. (a, b) Degeneracy within the 16- and 9-base motifs is illustrated at all positions by the stacked letters at each position. The relative height of each letter is proportional to its overenrichment in the motif. A line is boxed around rs3828903-G; this systemic lupus erythematosus-associated risk allele G is predicted to form the 8th and the second nucleotide in the motifs. (c) Altering the rs3828903 allele from rs3828903-G to rs3828903-A decreases the binding affinity for transcription factors CACD_2, Irf_disc4, Zfp740, and Zic_2 in HaploReg v4.1 database.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940546&req=5

fig1: Systemic lupus erythematosus-associated rs3828903 predicted to be part of the motifs for Zfp740 and Zic_2 in both HaploReg v4.1 and RegulomeDB databases. (a, b) Degeneracy within the 16- and 9-base motifs is illustrated at all positions by the stacked letters at each position. The relative height of each letter is proportional to its overenrichment in the motif. A line is boxed around rs3828903-G; this systemic lupus erythematosus-associated risk allele G is predicted to form the 8th and the second nucleotide in the motifs. (c) Altering the rs3828903 allele from rs3828903-G to rs3828903-A decreases the binding affinity for transcription factors CACD_2, Irf_disc4, Zfp740, and Zic_2 in HaploReg v4.1 database.
Mentions: In HaploReg v4.1 database, rs3828903 was predicted to locate in promoter histone marks, enhancer histone marks, DNase, proteins bound, and motifs changed regions within MICB. Four binding site motifs span the rs3828903 region for binding by the transcription factors (TFs) CACD_2, Irf_disc4, Zfp740, and Zic_2. The differences between the LOD scores for the alleles A and G (reference) were −3.8, −1.9, −6.4, and −2.8 for CACD_2, Irf_disc4, Zfp740, and Zic_2, respectively (Figure 1). Therefore, this model predicted a higher affinity to TFs for allele G (risk) relative to allele A. Also, in RegulomeDB database, rs3828903 showed a high score (1f, eQTL + TF binding/DNase peak). Consistent with the HaploReg v4.1 database, the motifs for binding by the TFs Zfp740 and Zic_2 have also been observed in RegulomeDB database (Figure 1), suggesting its potential role for gene expression regulation.

Bottom Line: In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)).Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Renal Division, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing 100034, China.

ABSTRACT
Objectives. The variant rs3828903 within MICB, a nonclassical MHC class I chain-related gene, was detected to contribute to systemic lupus erythematosus (SLE) in a Caucasian population. This study aimed to investigate the association in a northern Han Chinese population. Methods. We recruited 1077 SLE patients and 793 controls for analysis. rs3828903 was genotyped by TaqMan allele discrimination assay. Using the public databases, its functional annotations and gene differential expression analysis of MICB were evaluated. Results. Significant association between the allele G of rs3828903 and risk susceptibility to SLE was observed after adjusting for sex and age (P = 1.87 × 10(-2)). In silico analyses predicted a higher affinity to transcription factors for allele G (risk) and cis-expression quantitative trait loci (cis-eQTL) effects of rs3828903 in multiple tissues (P ranging from 2.79 × 10(-6) to 6.27 × 10(-38)). Furthermore, higher mRNA expressions of MICB were observed in B cells, monocytes, and renal biopsies from SLE patients compared to controls. Conclusion. An association between rs3828903 and susceptibility to SLE has been detected in a Chinese population. This together with the functional annotations of rs3828903 converts MICB into a main candidate in the pathogenesis of SLE.

No MeSH data available.


Related in: MedlinePlus