Interleukin 6 Promoter Polymorphisms in Normal Han Chinese Population: Frequencies and Effects on Inflammatory Markers

Pan, Min; Gao, Shu-Ping; Jiang, Min-Hui; Guo, Jing; Zheng, Jie; Zhu, Jianhua

doi:10.2310/jim.0b013e318206ffad

Cited by 21 publications

(26 citation statements)

References 55 publications

(84 reference statements)

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“…This finding is consistent with a previous report that the G-to-C polymorphism is extremely rare in Chinese [19]. In Japan only -174 GG genotype was detected, and the frequencies of -572 CC, GC and GG genotypes were 50%, 45% and 5%, respectively [20].…”

Section: Discussionsupporting

confidence: 82%

Association of IL-6 C-572G Gene Polymorphism with Anti-E Production

Lin

Lee

Liu

et al. 2017

Transfus Med Hemother

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Background: Interleukin 6 (IL-6) is involved in regulation of immunoglobulin production. The aim of this study was to investigate the association between IL-6 single nucleotide polymorphisms (SNPs) in the IL-6 promoter and anti-E in red blood cell (RBC) transfusion recipients. Methods: 50 healthy subjects, 54 patients with RBC alloantibody anti-E (responders), and 45 patients without alloantibody (non-responders) were recruited. All patients were E antigen-negative. Results: All healthy subjects and patients had GG at -174 position of IL-6 gene. In our healthy subjects, the frequency of the -572 CC genotype was 58%, that of the -572 CG genotype 38%, and that of the -572 GG genotype 4%. The frequency of G allele of -572 SNP in responders was significantly higher than that in non-responders, (31.5 vs. 16.7%; p = 0.020). The frequency of -572 G-positive genotypes (CG and GG) in responders was also significantly higher than that in non-responders, (55.6 vs. 31.1%; p = 0.016). The relative risk of RBC alloimmunization for patients with the -572 G-positive genotype was significantly higher than that of patients with the -572 CC genotype, (1.771 vs. 0.640; p = 0.016). Conclusion:IL-6 C-572G gene polymorphism is significantly associated with anti-E production, with the allele G as a risk allele.

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Section: Discussionsupporting

confidence: 82%

Association of IL-6 C-572G Gene Polymorphism with Anti-E Production

Lin

Lee

Liu

et al. 2017

Transfus Med Hemother

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“…Our metaanalysis of 83 studies involving 44,735 cases and 60,747 controls did not show a significant association between the -174G>C polymorphism and cancer risk, including lung cancer (Liu et al 2012). Of note, the -174C allele is extremely rare in Asian, including Chinese (Gu et al 2008; Lim et al 2002; Zhai et al 2001; Pan et al 2011). …”

Section: Discussionmentioning

confidence: 99%

“…Given the facts that haplotypes have more power to detect associations with risk of complex diseases than single polymorphism (Johnson et al 2001; Manolio et al 2008) and the G to C polymorphism at -174 of IL-6 is extremely rare in Asian, including Chinese (Gu et al 2008; Lim et al 2002; Zhai et al 2001; Pan et al 2011), we decided to examine the association of IL-6 haplotypes consisting of the two functional polymorphisms of IL-6 promoter (-6331T>C and -572C>G) with risk of lung cancer and to define the functional relevance of risk haplotypes.…”

Section: Introductionmentioning

confidence: 99%

A two-SNP IL-6 promoter haplotype is associated with increased lung cancer risk

Chen

Liu

Yang

et al. 2012

J Cancer Res Clin Oncol

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Background Aberrant expression of interleukin-6 (IL-6) may play an important role in lung carcinogenesis. Whether IL-6 promoter haplotypes are associated with lung cancer risk and their functions have not yet been studied. We tested the hypothesis that single-nucleotide polymorphism (SNP) and/or haplotypes of IL-6 promoter are associated with risk of lung cancer. Methods Two functional IL-6 promoter SNPs (-6331T>C and -572C>G) were genotyped in the discovery group including 622 patients and 614 controls, and the results were replicated in an independent validation group including 615 patients and 638 controls. Luciferase reporter gene assays were conducted to examine the function of IL-6 promoter haplotypes. Results None of the functional IL-6 promoter SNPs were associated with lung cancer risk in either study. However, a two-SNP CC (-6331C and -572C) IL-6 promoter haplotype was significantly more common among cases than among controls in both groups (P = 0.031 and P = 0.035, respectively), indicating that this haplotype is associated with increased lung cancer risk {adjusted odds ratio [OR], 1.56 [95 % confidence interval (95 % CI), 1.04–2.34] and 1.51 [95 % CI, 1.03–2.22], respectively}. Combined analysis of both studies showed a strong association of this two-SNP haplotype with increased lung cancer risk (adjusted OR, 1.53; 95 % CI, 1.16–2.03; P = 0.003). Comparably, luciferase reporter assays of A549 lung cancer cell lines transfected with the CC haplotype revealed that the two-SNP haplotype had significantly higher IL-6 transcriptional activity compared with cells transfected with the common haplotype. Conclusions This is the first evidence of identifying an IL-6 promoter haplotype (CC) associated with increased risk of lung cancer.

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“…7,39,40 The association of IL-6 polymorphism with higher serum CRP concentration maybe due to an increase in IL-6 gene transcription and the consequent effects of increasing levels of IL-6 on CRP gene expression. 9 Our previous report 9 along with the studies conducted in Japanese and Koreans 18,[41][42][43][44][45] indicated that IL-6 À634G allele was associated with higher circulating levels of IL-6 and CRP in eastern Asians. However, assessment of serum IL-6 and CRP levels concordant with IL-6 À634C/G polymorphism in patients with AF, especially in patients with AF with LA thrombus, is required in further study.…”

Section: Discussionmentioning

confidence: 95%

The Association of Interleukin 6−634C/G Polymorphism With Left Atrial Thrombus and Severe Spontaneous Echocontrast in Patients With Atrial Fibrillation

Deng

Jiang

Zhu

et al. 2012

Clin Appl Thromb Hemost

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Atrial fibrillation (AF) not only is an independent risk factor for death but also confers significant risk of morbidity from stroke associated with left atrial thrombus. The association of interleukin 6 (IL-6) polymorphism with thrombus in AF has not been investigated before. We carried out a case-control study in Han Chinese. The IL-6 -634C/G genotypes of 31 patients with thrombus and 45 patients without thrombus were detected by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of the IL-6 genotypes (CC, CG, and GG) were 29.03%, 54.54%, and 16.13% for the patients with thrombus, and 55.56%, 40.00%, and 4.44% for the patients without thrombus, respectively (P = .0391). Compared with the CC genotype, the G allele carriers (CG + GG) had a 2.79-fold increased risk of thrombus or severe spontaneous echocontrast (SEC). These results suggest that IL-6 -634C/G polymorphism is associated with thrombus and severe SEC, and the G allele is an independent risk for thrombus and severe SEC in Han Chinese patients with AF.

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Interleukin 6 Promoter Polymorphisms in Normal Han Chinese Population: Frequencies and Effects on Inflammatory Markers

Abstract: IL-6 -174G/C and -597G/A are rare, but -634C/G is common in Han Chinese population, and the -634G allele is associated with circulating levels of IL-6 and C-reactive protein.

Cited by 21 publications

References 55 publications

Association of IL-6 C-572G Gene Polymorphism with Anti-E Production

Association of IL-6 C-572G Gene Polymorphism with Anti-E Production

A two-SNP IL-6 promoter haplotype is associated with increased lung cancer risk

The Association of Interleukin 6−634C/G Polymorphism With Left Atrial Thrombus and Severe Spontaneous Echocontrast in Patients With Atrial Fibrillation

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