THE −174 G TO C POLYMORPHISM OF INTERLEUKIN-6 GENE IS VERY RARE IN KOREANS

doi:10.1006/cyto.2002.1951

Cytokine

Volume 19, Issue 1, July 2002, Pages 52-54

https://doi.org/10.1006/cyto.2002.1951 Get rights and content

Abstract

The proinflammatory cytokine, interleukin-6 (IL-6), seems to be involved in the pathogenesis and progression of IgA nephropathy. Moreover, the transcriptional activity of the IL-6 gene and the plasma levels of IL-6 protein are associated with a single G/C base exchange polymorphism at position −174 of the IL-6 gene promoter. Using PCR-RFLP and PCR product sequencing, we examined the −174 polymorphism in 104 IgA nephropathy patients and in 53 of the normal Korean population. Only 2 GC heterozygous variants and no CC homozygous variants were found (C allele frequency=0.006). These results suggest that the frequency of the C allele in the Korean population is considerably lower than in the Caucasian population, and it appears that the −174 G to C polymorphism of IL-6 is very rare in Eastern Asians. And, the IL-6 polymorphism at −174 is unlikely to contribute significantly to susceptibility to or the progression of IgA nephropathy in Koreans.

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Cited by (58)

Interleukin-6 Receptor Asp358 A>C Polymorphism Is Associated With Postoperative Atrial Fibrillation
2021, Annals of Thoracic Surgery
Citation Excerpt :
However, in our study, neither −174G>C nor −597G>A was associated with IL-6 at any time point in patients with or without POAF. The lack of associations may lie in the finding that the rates of the C allele of IL-6 −174G>C and the A allele of IL-6 −597 G>A were minimal in the Chinese Han population, an observation that concurs with previous findings showing that the C allele of −174G>C is very rare in East Asians.35,36 Thus, the IL-6 −174G>C or −597 G>A SNPs are unlikely to contribute significantly to POAF susceptibility in the Chinese Han population.
This study examined the associations of single-nucleotide polymorphisms in the interleukin-6 receptor gene (Asp358 A>C) and the interleukin-6 promoter (−174G>C and −597G>A) with interleukin-6 levels and postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG).
The study enrolled 371 Chinese Han patients who were undergoing CABG. Serum interleukin-6 levels were measured preoperatively and at 6, 12, and 18 hours postoperatively. Genotypes for the 3 polymorphisms were determined.
Overall, POAF developed in 30.2% of patients. The CC genotype and C allele frequencies for the interleukin-6 receptor Asp358 A>C polymorphism were significantly higher in patients with POAF than in patients without POAF (P = .003), and the interleukin-6 levels were significantly higher in patients with the CC genotype compared with A allele carriers at 6, 12, and 18 hours in the overall cohort and at 12 and 18 hours in the POAF subgroup, but there were no significant differences in the non-POAF subgroup. However, the allele and genotype frequencies of the interleukin-6 −174G>C and −597G>A polymorphisms were similar among groups, and there were no differences in interleukin-6 levels at any time point between the C/A allele carriers and the patients with GG genotypes. Univariate analysis showed that the CC genotype for interleukin-6 receptor Asp358 A>C, age, and history of cerebrovascular disease were associated with POAF. Multivariable regression showed that the CC genotype was independently related to the development of POAF (odds ratio, 2.01; 95% confidence interval: 1.15 to 3.52; P = .014).
The interleukin-6 receptor Asp358 A>C polymorphism may contribute to genetic susceptibility to POAF after CABG.
Meta-analysis of association between il-6-174 g/c polymorphism and female infertility related disorders
2020, Journal of Reproductive Immunology
Citation Excerpt :
For instance, IL-6-174 GG genotype was found to be more prevalent in African-American and non-Caucasian population (DeMichele et al., 2003) while IL-6-174 CC genotype was found more prevalent in the Caucasian ethnic group. This same polymorphism was not detected among the Japanese population (Nakajima et al., 1999; Kitamura et al., 2002) and was extremely rare in Chinese (Zhai et al., 2001) and Korean population (Lim et al., 2002). Overall analyses of the pooled OR showed favourable association between the polymorphism and the disorders under allele and dominant model, but not under the recessive model.
Female infertility continues to increase in prevalence annually and factors causing it need to be researched. As IL-6-174 G/C polymorphism is known to alter the plasma levels of IL-6, abnormal levels of IL-6 found in infertile females could be due to genetic reasons. With the understanding of the importance of IL-6 in reproductive physiology, several individual studies done so far to find the association of this polymorphism with female infertility related disorders were systematically combined for meta-analysis. Articles were searched using electronic data base sources and were included based on specific criteria. Finally, eight articles which includes polycystic ovarian syndrome (PCOS; n = 4), endometriosis (n = 3) and tubal damage (n = 1) were selected for the analysis. Results showed statistically signiﬁcant heterogeneity across studies under the allele model (p < 0.0001, I² = 78 %) and dominant model (p < 0.00001, I² = 82%) but not under recessive model (p = 0.31, I² = 16%). This difference could be possibly due to variation in ethnicity, lifestyle, age or BMI related factors. The pooled odds ratio under the three genetic models were 0.87(CI = 0.75-1.02), 0.77 (CI = 0.63-0.94) and 1.05 (CI = 0.76-1.46) respectively. Sub group analysis showed statistical significant (P < 0.01) for PCOS under allele and dominant model, but not for endometriosis and tubal damage. By this meta-analysis, we can say that IL-6-174 G/C polymorphism can be considered as a potential genetic marker for PCOS but not for endometriosis and tubal damage disorders. However, more studies with adequate sample sizes are required to be done in endometriosis, tubal disease and other female infertility disorders to arrive at a definite conclusion.
Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10) polymorphisms in the risk of oral precancerous lesions in Taiwanese
2014, Kaohsiung Journal of Medical Sciences
Citation Excerpt :
A G/C SNP in the promoter region (−174) of IL-6 was shown to affect transcription and alter plasma IL-6 levels. As reported in the literature, the IL-6 variant genotype (C/C) frequency varied dramatically among different ethnic groups; for example, it is very low in Asian populations [17]. Our control frequency, compared with other studies about Southern Chinese population [18], is slightly higher.
Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs). Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN)-γ, transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A), TGF-β1 (codons 10 T/C and 25 G/C), TNF-α (−308 G/A), IL-6 (−174 G/C), and IL-10 (−1082 A/G, –819 T/C, and −592 A/C)]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ²) test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (−308) polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004). Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25) polymorphism was also significantly associated with OPCLs (p < 0.001). The IL-6 polymorphism was significantly associated with OPCLs. There are significant differences in the distribution of CC, GC, and GG genotypes between OPCL patients and controls (p < 0.001). Patients with the CC or GC genotype had a 35- or 20.59-fold increased risk of OPCLs. There were no significant differences in the distribution of IL-10 and IFN-γ genotypes between different groups of control individuals and OPCL patients. The IL-6, TGF-β1, and TNF-α gene polymorphisms may have a significant association with the development of OPCLs.
Negative emotions predict elevated interleukin-6 in the United States but not in Japan
2013, Brain, Behavior, and Immunity
Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health.
The G to A polymorphism at -597 of the interleukin-6 gene is extremely rare in southern Han Chinese
2011, Cytokine
Citation Excerpt :
Associations of the -174G/C polymorphism with circulating level of IL-6 have been reported in various studies [21–23]. The frequency of the C allele at the -174G/C is very high in Caucasians [17], but is rarely found in eastern Asian populations [24–26]. Based on these findings, we detected -597G/A (rs1800797) polymorphism in the IL-6 gene promoter region in patients with essential hypertension (EH) and healthy individuals in Jiangsu area (south of China).
Interleukin-6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes including essential hypertension (EH). Associations of the IL-6 promoter region polymorphisms with circulating level of IL-6 have been reported in various studies. We detected the IL-6-597G/A polymorphism in 246 EH patients and 194 healthy controls from Jiangsu area (south of China). Individuals all carried the GG wild genotype, no GA or AA genotypes were found. Our results suggest that IL-6-597G/A polymorphism is extremely rare and unlikely to be contributing significantly to disease susceptibility in southern Han Chinese.
The interleukin-6 gene -572C/G promoter polymorphism modifies Alzheimer's risk in APOE e{open}4 carriers
2010, Neuroscience Letters
Inflammatory response is involved in the etiopathology of Alzheimer's disease (AD). Interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, was reported to be associated with both increased Aβ aggregation and the appearance of hyperphosphorylated tau in AD brain. To explore the association of genetic variants in the promoter of IL-6 gene with sporadic AD (SAD), a case–control study was conducted in a North Chinese Han population. A systematic screening of IL-6 promoter was performed using direct sequencing and two polymorphisms were obtained including −572C/G (rs1800796) and −384A/T (rs7802308). Definitive genotyping of these markers and apolipoprotein E (APOE) polymorphism were surveyed in 341 SAD patients and 421 controls. The results revealed no significant differences in the distributions of alleles or genotypes between SAD and control groups. However, there was an interaction between −572C/G and APOE genotypes (P = 0.016) using logistic analysis. In the subjects with APOE ɛ4, there were significant differences in the allele (P = 0.004) and genotype (P = 0.004) distributions of −572C/G polymorphism between SAD and control groups. The −572CC genotype increased risk for AD by 3.301-fold (Wald = 11.093, adjust OR = 3.301, 95% CI = 1.635–6.665, P = 0.001) compared to CG + GG genotype. The present results suggest the −572 polymorphism could modify the risk for SAD in APOE ɛ4 carriers.

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^f1: Correspondence to: Dong-Wan Chae, M.D., Department of Internal Medicine, Kangdong Sacred Heart Hospital, 445 Gil-Dong, Kangdong-Gu, Seoul 134-701, Korea. Tel: +82-2-22242544; Fax: +82-2-4786925; E-mail:[email protected]

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Short CommunicationsTHE −174 G TO C POLYMORPHISM OF INTERLEUKIN-6 GENE IS VERY RARE IN KOREANS

Abstract

Kidney Int

Kidney Int

Lancet

Am J Kidney Dis

Blood

Blood

The effect of novel polymorphisms in the interleukin 6 (IL-6) gene on IL-6 transcription and IL-6 levels, and an association with systemic-onset juvenile chronic arthritis

J Clin Invest

Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren's syndrome and correlate with the clinical manifestations of the disease

Rheumatology

Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women

Genes Immun

Short Communications
THE −174 G TO C POLYMORPHISM OF INTERLEUKIN-6 GENE IS VERY RARE IN KOREANS