Cytokine Gene Single Nucleotide Polymorphisms Research Articles

Contribution of polymorphic variants of pro- and anti-inflammatory cytokine genes to the development of occupational lung dust pathology in miners

Introduction. The formation and progression of occupational pathology of the bronchopulmonary system during prolonged contact with fibrogenic dust are closely related to changes in the concentration of certain pro- and anti-inflammatory cytokines in the bloodstream. The change in cytokine expression is due to the presence of polymorphism of certain genes, which results in quantitative or structural changes in proteins that can affect the course and outcome of dust lung diseases.
 The study aims to determine the associations of single-nucleotide polymorphisms of cytokine genes with the formation of occupational dust pathology of the lungs.
 Materials and methods. Scientists examined 140 coal mine workers who had been exposed to high concentrations of coal and stone dust for a long time. We divided the study participants into 2 groups. The main group included 75 miners with a previously established diagnosis of "dust pathology of the lungs", the comparison group consisted of 65 men working in the same sanitary and hygienic conditions, but without an established occupational disease of the bronchopulmonary system. The research groups are comparable by gender, age and ethnicity. The scientists carried out genotyping by allele-specific polymerase chain reaction in real time.
 Results. Experts have identified a number of gene polymorphisms associated with the risk of developing occupational pathology of the bronchopulmonary system as a result of exposure to fibrogenic dust in Kuzbass miners. They also found that the following markers predispose to the formation of occupational lung pathology in miners: allele C and heterozygous genotype C/T of the polymorphic locus rs1800896 of the IL-10 gene, allele C of the polymorphism rs1800795 of the IL-6 gene, homozygous genotype T/T of the IL-4 gene (rs2243250). In turn, the T allele and the homozygous T/T genotype of the rs1800896 polymorphism of the IL-10 gene, as well as the G allele of the rs1800795 polymorphic locus of the IL-6 gene have a protective effect on the development of occupational lung dust pathology.
 Limitations. The conducted study has limitations in the form of a relatively small sample size and the lack of quantitative determination of the concentration of cytokines in the blood.
 Conclusion. The results of the conducted studies indicate the contribution of polymorphic variants of the genes of the studied pro- and anti-inflammatory cytokines to the formation of genetic predisposition and resistance to the development of dust pathology of the lungs of professional genesis. With the help of the obtained informative markers, it is possible to assess the risk of developing dust lung diseases in miners working in contact with high concentrations of coal-rock dust.
 Ethics. The Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases has approved the study. The examination of patients was carried out on the basis of ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical principles of conducting Scientific medical research with human participation" as amended in 2013 and "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation No. 266 dated 06/19/2003. The study was conducted with the written consent of the subjects.

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Полиморфизм генов цитокинов, ассоциированных с инфекционным эндокардитом

Infectious endocarditis is a disease with the primary pathogen localization on the heart valves and the mural endocardium, occurring with the possible generalization of the septic process and the immunopathological changes that are very significant in the disease manifestation and course. Based on the fact that 30–50% of cases concerning infectious endocarditis develop without the obvious involvement of standard risk factors (invasive procedures or endovascular disorders), it can be assumed that molecular genetic factors are involved in the disease pathogenesis and its complications. There is reason to believe that the activation of inadequate inflammation in response to the microbial invasion may be due to polymorphism in the genes controlling the cytokine activity. However, the information available today on the various cytokines level and the gene polymorphism in various clinical variants of infectious endocarditis is very limited and commonly contradictory, which requires a deeper study of the pathogenetic association of infectious endocarditis with cytokine genetic defects. In this regard, the expansion of ideas concerning the of cytokine gene polymorphisms in the form of point mutations (SNP), capable of regulating the intensity of cytokine expression and their biological effects, will allow to predict the risk of infectious endocarditis, the severity of its course, the risk of possible complications, as well as the individual treatment tactics for patients. KEYWORDS: infectious endocarditis, clinical variants, complications, cytokines, cytokine genes, genetic polymorphism, pathogenesis, diagnosis. FOR CITATION: Samoylenko E.S., Kolesnikova N.V. Cytokine gene single nucleotide polymorphisms associated with infectious endocarditis. Russian Medical Inquiry. 2023;7(7) (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-2.

A Pilot Study of Associations Between the Occurrence of Palpitations and Cytokine Gene Variations in Women Prior to Breast Cancer Surgery.

Palpitations are common and have a negative impact on women's quality of life. While evidence suggests that inflammatory mechanisms may play a role in the development of palpitations, no studies have evaluated for this association in patients with breast cancer who report palpitations prior to surgery. The purpose of this pilot study was to evaluate for associations between the occurrence of palpitations and single nucleotide polymorphisms (SNPs) in genes for pro- and anti-inflammatory cytokines, their receptors, and transcriptional regulators. Patients were recruited prior to surgery and completed a self-report questionnaire on the occurrence of palpitations. Genotyping of SNPs in cytokine genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of palpitations and SNPs in fifteen candidate genes. Of the 82 SNPs evaluated in the bivariate analyses, eleven SNPs in 6 genes were associated with the occurrence of palpitations. After controlling for functional status, the occurrence of back pain, and self-reported and genomic estimates of race/ethnicity, 3 SNPs in 3 different genes (i.e., interleukin (IL) 1-beta (IL1B) rs1143643, IL10 rs3024505, IL13 rs1295686) were associated with the occurrence of palpitations prior to surgery (all p ≤ .038). While these preliminary findings warrant replication, they suggest that inflammatory mechanisms may contribute to the subjective sensation of palpitations in women prior to breast cancer surgery.

Distribution of 22 Single Nucleotide Polymorphisms in 13 Cytokine Genes in Malays, Chinese, and Indians in Peninsular Malaysia.

Introduction: Cytokines are cell signaling glycoproteins that are particularly important in immunity and inflammatory responses. Therefore, variations, such as single nucleotide polymorphisms (SNPs), in genes encoding for cytokines may have important consequences for their roles in health. Materials and Methods: A total of 222 unrelated, healthy, and un-admixed Malays (n = 97), Chinese (n = 77), and Indians (n = 48) with a median age of 30 years old (range 21-50) were typed for 22 cytokine gene SNPs: IL-1α -889 T/C, IL-1β (-511 T/C, +3962 T/C), IL-1R pst1 1970 T/C, IL-1RA mspa1 11100 T/C, IL-4Rα +1902 G/A, IL-12 - 1188 C/A, IFN-γ +874 A/T, TGF-β (cdn 10 C/T, cdn 25 G/C), TNF-α (-308 A/G, -238 A/G) IL-2 (+166 G/T, -330 T/G), IL-4 (-1098 T/G, -590 T/C, -33 T/C), IL-6 (-174 C/G, nt565 G/A), and IL-10 (-1082 G/A, -819 C/T, -592 A/C). This involved using well-established polymerase chain reaction procedures with sequence-specific primers and restriction fragment length polymorphism methods. Results: The majority of the screened cytokine gene SNPs are polymorphic in all three ethnicities. Exceptions include TGF-β cdn 25 (G/C), IL-1β +3962 (T/C), and TNF-α -238 (A/G), which were all observed to be monomorphic in Malays, Chinese and Indians. Many of the analyzed cytokine gene SNP genotypes deviated from Hardy-Weinberg equilibrium and the three ethnic study groups were all well-separated from reference Asian, African and European populations in a principal component analysis plot. Conclusion: We successfully typed 22 SNPs in 13 cytokine genes from genetic material collected from unrelated and un-admixed Malay, Chinese and Indian individuals in Peninsular Malaysia. These new cytokine gene population datasets reveal interesting contrasts with other populations.

Association of Cytokine Gene Polymorphisms with Prostate Cancer Risk from a Study in Central China.

Our study intended to investigate five cytokine gene single nucleotide polymorphisms (SNPs) and their associations with prostate cancer risk. Genotypes of five cytokine gene SNPs were detected by MassARRAY for blood samples from a group of patients with prostate cancer (n = 90) and a control group (n = 140) in central China. The differences in tumor clinical stages, Gleason scores, and PSA values in patients with prostate cancer were also investigated. The frequencies of the five cytokine gene SNPs (L-1β rs16944, IL-4 rs2070874, IL-4rs2227284, IL-16 rs7175701, and IL-16 rs11556218) genotypes were not found to be significantly mutated in prostate cancer patients compared with the control group. In addition, for five cytokine gene SNPs genotypic comparisons, patients with different Gleason scores, clinical stages, and PSA values were grouped into two subgroups. There was also no statistically significant association in all these subgroups. Our study suggests that cytokine gene polymorphisms may not be a risk factor for prostate cancer in a central Chinese population. Nevertheless, more large-scale studies on the Chinese population are necessary to examine our conclusions. The discovery of cytokine gene polymorphisms related to prostate cancer could update our understanding of the etiology and improve our knowledge of the early detection, diagnosis, and treatment of prostate cancer.

Однонуклеотидные полиморфизмы генов цитокинов и их роль в патогенезе сердечных, сосудистых и легочных заболеваний

Однонуклеотидные полиморфизмы генов цитокинов и их роль в патогенезе сердечных, сосудистых и легочных заболеваний

Current research on cytokine gene single nucleotide polymorphisms of Behcet's syndrome

Behcet's syndrome (BS) is characterized by systemic vasculitis with unknown etiology. There is evidence that more than one mechanism underlies the pathogenesis of BS, involving genetic factors and environmental stimuli. Although human leucocyte antigen-B51 is by far the most strongly associated genetic factor to BS, it accounts for less than 20% of the genetic risk, which indicates that other genetic factors remain to be discovered. Cytokines are signal molecules of the immune system which modulate the inflammatory process of nearly all immune response. The single nucleotide polymorphism (SNP) of cytokine gene have been associated with BS in many studies, involving T helper cell 1-type cytokines, interleukin 1 cytokine, interleukin 17 and chemotactic cytokine. The impact of different SNPs on BS varies, most of which affect the risk of disease, while the remaining affect the phenotype, the cumulative effect of these minor genes (SNPs) might be the genetic mechanisms of BS pathogenesis. (Chin J Ophthalmol, 2020, 56: 876-880).

Cytokine genes multi-locus analysis reveals synergistic influence on genetic susceptibility in Indian SLE – A multifactor-dimensionality reduction approach

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear etiology. Several loci associated with genetic susceptibility for lupus have been described. However, it lacks reports on cytokine gene-gene interactions among SLE patients from Asian population. Epistasis interaction among single nucleotide polymorphisms (SNPs) of cytokine genes in Indian SLE patients was tested using multifactor-dimensionality reduction (MDR) analysis. A total of fourteen SNPs lacking linkage disequilibrium among different cytokines genes were genotyped in a cohort of 200 SLE patients and 201 healthy individuals as controls of Indian origin. A high degree of synergism among Lymphotoxin-α (LT-α), Interleukin-1β (IL-1β) and Interleukin-10 (IL-10) gene polymorphisms was detected in our SLE patients. Furthermore, by virtue of biological inter-relations among different cytokines, a high strength of interactions was observed among pro-inflammatory (IL-1β, IL-6) and anti-inflammatory (IL-10) cytokine gene SNPs. Also, among studied pro-inflammatory cytokines and chemokines, a strong synergistic effect among Tumor Necrosis Factor-α (TNF-α), LT-α and Monocyte Chemo-attractant Protein-1 (MCP-1) SNPs was occurred. A nature of strong interaction among the candidate cytokine genes may speculate a proactive role in causing genetic susceptibility to the disease in SLE patients with Indian origin.

Lack of association between interleukin 13, interleukin 4 receptor alpha, andMS4A2 gene polymorphisms and asthma in adult Saudis

Objectives: Several genes, including interleukin-13 (IL13), MS4A2, and IL 4 receptor alpha (IL4Rα), have been shown to associate with the inflammatory process in asthma. We investigated the possible association between asthma and five single-nucleotide polymorphisms (SNPs) in the IL13, IL4Rα, and MS4A2 gene in comparison with the level of the IL-13 protein in the Saudi asthmatics and controls. Subjects and Methods: The study group included 50 adult asthmatic patients and 50 normal healthy controls. Blood was extracted, and DNA was prepared. Genotyping was performed on DNA using direct sequencing for four SNPs (rs20541, rs1800925, rs1801275, and rs569108), and real-time polymerase chain reaction allelic discrimination to study rs1805010 polymorphism. Levels of IL-13 were measured in plasma using (enzyme-linked immunosorbent. Genotype and allele frequencies were calculated for each SNP. Results: The results showed that GG genotype of rs1801275 in the IL4Rα gene was more common in the asthmatic patients compared to the control group, though the results did not show any statistical significance (P G transition nonsynonymous mutation, resulting in the substitution of glutamine by arginine showed an association, but it was statistically not significant. Interestingly, presence of the mutant allele of both SNPs of IL-13 gene significantly elevated IL-13 level. Comparison of the Saudi results with those of other populations, showed several significant differences. We conclude that further more detailed studies are necessary in Saudis to identify the contribution of SNPs in cytokine genes in asthma development.

Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis

ABSTRACT Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools. Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case–control studies. Results: A total of 35 relevant case–control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA −308 G > A and IL-10 − 1082A>G) and ZNF263 (TNFA −238 G > A) transcription factors binding. Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.

Polymorphisms of cytokine genes and tuberculosis in two independent studies

Cytokine gene single nucleotide polymorphisms (SNPs) can influence cytokine levels, which may be associated with tuberculosis (TB) susceptibility. There is evidence that interleukin 1B (IL1B), tumor necrosis factor-alpha (TNF-alpha), and IL6 may be involved in the progression of TB. Using a self-validating case-control design, we selected eleven functional SNPs in IL1B, TNF and IL6 to detect their association with TB in Chinese Han and Tibetan populations. The associations between SNPs and TB were estimated by computing the odds ratios (ORs) and 95% confidence intervals (95% CI) using logistic regression analyses. We found that the IL1B rs16944 polymorphism was associated with decreased risk of TB in the two studies. The G allele at rs2069837 of IL6 was significantly more common in controls than in TB patients in the Han population. Moreover, TNF rs1799964 and rs1800630 were risk factors for susceptibility to TB, which were validated in the Chinese Tibetan population. In addition, TNF rs1799724 and rs1800629 were associated with TB, but only in the Tibetan population. In conclusion, SNPs of the IL1B and TNF gene were associated with TB susceptibility in Chinese Han and Tibetan populations. IL6 polymorphism may be considered as a protective factor for TB in the Chinese Han population, but not the Tibetan population.

Cytokine gene variations and their impact on serum levels of IFN-γ, IL-2, IL-4, IL-10 and IL-12 among Iraqi Arabs

The impact of ten cytokine gene single nucleotide polymorphisms [SNPs: IFNG+874 (rs2430561), IL2+166 (rs2069763), IL2−330 (rs2069762), IL4−33 (rs2070874), IL4−590 (rs2243250), IL4−1098 (rs2243248), IL10−592 (rs1800872), IL10−819 (rs1800871), IL10−1082 (rs1800896), and IL12B−1188 (rs3212227)] on serum level of IFN-γ, IL-2, IL-4, IL-10, and IL-12 was determined among 127 Iraqi Arabs (60 males and 67 females). Their age mean ± SD was 24.1 ± 15.5 years. The results revealed that IFN-γ, IL-2, IL-4, and IL-10 levels showed no gender-associated variation, while IL-12 level was significantly increased in females compared to males. Alleles of the ten SNPs showed polymorphic frequencies, and C allele of IL12B−1188 SNP recorded the lowest frequency (27.2%). With respect to the impact of SNP genotype on cytokine level, only IL2+166 (total sample and males), IL4−33, and IL4−590 (total sample and females) SNPs showed a significant impact on the level of their corresponding cytokines (IL-2 and IL-4). In conclusion, a positive influence of IL2+166, IL4−590, and IL4−33 SNP genotypes on IL-2 and IL-4 levels is suggested, and such influence was gender-dependent.

Association of T Helper 1 Cytokine Gene Single Nucleotide Polymorphisms with Ulcerative Colitis and Crohn’s Disease

Background: Inflammatory bowel disease (IBD) mostly comprised of Crohn’s disease (CD) and ulcerative colitis (UC) is a condition arising from the combined effects of genetic, environmental, and immunological factors. IBD is associated with inflammation and altered cytokine profile. Objective: This study was aimed at assessing the association between T helper type 1 (Th1) cytokine polymorphisms (interferon gamma [IFN-γ] +874 A/T, interleukin-12 [IL-12] –1188 A/C, IL-2 –330 G/T, IL-2 +166 G/T) and susceptibility to and clinical features of IBD. Methods: The study population was composed of 75 IBD patients (40 CD patients and 35 UC patients) and 140 healthy controls. Genotyping was performed using polymerase chain reaction with sequence-specific primers. Results: The A allele of IFN-γ +874 polymorphism was overrepresented in the whole population of patients with IBD (OR 1.63; 95% CI 1.08–2.47; p = 0.020) and as well in the subpopulation of patients with CD (OR 2.14; 95% CI 1.26–3.63; p = 0.004), but not in UC. Multiple pairwise comparisons indicated that genotypes of single nucleotide polymorphisms (SNPs) within the IL-2 and IFN-γ genes are correlated with IBD, CD, and UC, while neither allele nor genotype frequency of th1 IL-12 –1188 polymorphism was associated with IBD, CD, or UC. Haplotype analysis also revealed that the presence of IL-2 –330/+166 TG haplotype versus the remaining haplotypes (GG, TT, and GT) is a protective factor against IBD (OR 0.62; p = 0.046). Conclusions: The present study reports (for the first time) significant associations between SNPs within the IFN-γ and IL-2 genes and IBD.

A Role of Cytokine Gene Polymorphisms in Cognitive Functioning.

The changes in cognitive functions that occur with aging and in various pathological conditions are a subject of growing interest. Experimental and clinical data justify the hypothesis about the influence the immune system exerts on cognitive processes. The balance between pro-inflammatory and anti-inflammatory cytokines has been established as a necessary factor for normal cognitive functioning. Cytokine production is under strong genetic control and various single nucleotide polymorphisms (SNPs) in cytokine genes have been described. As cytokine SNPs have been demonstrated to affect the gene expression or the functional activity of the immune protein this logically led to the suggestion about the role of these polymorphisms in cognitive functioning. Studies exploring the association between different genetic variants of cytokine gene polymorphisms and cognitive abilities in healthy subjects and in demented patients show divergent results. The review of relevant literature suggests that SNPs implement their effect on cognition in large interactions with each other, as well as with many other factors, some of which still remain to be identified. This article summarizes the contemporary knowledge about the correlations between SNPs in cytokine genes and cognitive status in humans. Further research is needed to determine the precise role and the molecular mechanisms of action of the SNPs in cognitive processes.

Polymorphisms of Cytokine Genes and Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS) is the endocrinopathy that affects women in their reproductive age. The physiopathology involves multifactorial mechanisms, including cytokine gene regulation. The review was conducted in the database PubMed, with articles published between 2005 and 2015. The selected studies evaluated the single-nucleotide polymorphisms (SNPs) of cytokines genes in association with PCOS. Twenty-four studies met the inclusion criteria and showed the SNPs of cytokines that were associated or not with PCOS. The disease susceptibility was associated with interleukin (IL) 1A, IL1B, IL1RN, and IL6 alleles and genotypes. The tumor necrosis factor (TNF) -1032 C/T genotype and C allele were risk factors and T/T genotype was a protector marker to disease. The IL18 SNPs were not associated with PCOS per se, but IL18-137 C and G alleles were related to the protection of insulin resistance and glucose tolerance, respectively. One research found association between TGFB1 and PCOS. However, the TNF -308, IL10, and interferon (IFN) SNPs did not appear to influence PCOS genetic susceptibility. This study sought to contribute and clarify the SNPs in cytokine genes that influence the development of PCOS. Most studies occurred in Asia; most SNPs studied were in IL1B -511, TNF -1031, and IL6-174; and most of them were associated with the susceptibility to PCOS development. Nevertheless, further investigations based on genome-wide association studies and cytokine gene SNPs are needed to better characterize the risk factors to PCOS.

Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population.

Background:Cytokine gene single nucleotide polymorphisms (SNPs) are widely used to study susceptibility to complex diseases and as a tool for anthropological studies.Materials and Methods:To investigate cytokine SNPs in an Iranian multi-ethnic population, we have investigated 10 interleukin (IL) SNPs (IL-1β (C-511T, T-31C), IL-2 (G-384T), IL-4 (C-590T), IL-6 (G-174C), IL-8 (T-251A), IL-10 (G-1082A, C-819T, C-592A) and tumor necrosis factor-alpha (TNF-α) (G-308A) in 415 Iranian subjects comprising of 6 different ethnicities. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium (HWE) were calculated by PyPop software. Population genetic indices including observed heterozygosity (Ho), expected heterozygosity (He), fixation index (FIS), the effective number of alleles (Ne) and polymorphism information content (PIC) were derived using Popgene 32 software. Multidimensional scaling (MDS) was constructed using Reynold's genetic distance obtained from the frequencies of cytokine gene polymorphism.Results:Genotypic distributions were consistent with the HWE assumptions, except for 3 loci (IL-4-590, IL-8-251 and IL-10-819) in Fars and 4 loci (IL-4-590, IL-6-174, IL-10-1082 and TNF-α-308) in Turks. Pairwise assessment of allelic frequencies, detected differences at the IL-4-590 locus in Gilakis versus Kurds (P = 0.028) and Lurs (P = 0.022). Mazanis and Gilakis displayed the highest (Ho= 0.50 ± 0.24) and lowest (Ho= 0.34 ± 0.16) mean observed heterozygosity, respectively.Conclusions:MDS analysis of our study population, in comparison with others, revealed that Iranian ethnicities except Kurds and Mazanis were tightly located within a single cluster with closest genetic affinity to Europeans.

Combined effects of six cytokine gene polymorphisms and SNP-SNP interactions on hepatocellular carcinoma risk in Southern Guangxi, China.

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-γ, IL-1β, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-γ-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

THE ROLE OF CYTOKINE GENES POLYMORPHISM IN HEPATITIS C VIRUS INFECTION

Abstract. The outcome of hepatitis C virus (HCV) infection depends on the immune response caused by the host genetic factors. Cytokines are key mediators of inflammation and development of specific immunity, which is responsible for the elimination of HCV. It has been found that the polymorphisms in several cytokine genes play role in human susceptibility to HCV infection, determine its differences in response to HCV and treatment-induced HCV clearance. This review summarizes the results of studies on the single-nucleotide polymorphisms of cytokine genes that complete our knowledge of the pathogenesis of HCV infection.

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Acute and chronic allograft rejections are important causes of morbidity following kidney transplantation that ultimately influence long term graft function. Cytokines are the key molecules known to regulate immune response towards alloantigen determining graft rejection or tolerance. Genetic variability including single nucleotide polymorphisms (SNPs) in the promoter and coding region of these genes is known to influence cytokine expression, and could therefore significantly impact the outcome of the alloimmune response. In this study, SNPs in cytokine genes namely Interleukin (IL)-12 (−1188 C/A), interferon (IFN)-g (+874 A/T), transforming growth factor (TGF)-b (C/T codon 10, G/C codon 25), tumor necrosis factor (TNF)-a (G/A −308, G/A −238), IL2 (T/G −330, G/T +160), and IL10 (G/A −1082, C/T −819, C/A −592) were determined in 182 patients undergoing renal transplantation from their live related and unrelated donors. Of these, 50 patients experienced acute rejection episodes (AR), 42 experienced chronic allograft nephropathy (CAN) (25 patients who had previous AR episodes and 17 without any AR episodes), while the remaining 115 patients had well functioning grafts (WFG). The high producer genotype TT of IFN-g showed a strong association with development of AR; while the AA genotype (low producer) conferred protection from AR (p < 0.0001) and CAN (p = 0.007). Similarly, genotype GG at codon 25 (high producer) of TGF-b, was associated with AR episodes (p < 0.05) and CAN (p < 0.05). The study highlights the clinical relevance of cytokine gene polymorphism as an important biomarker to predict acute rejection episodes and chronic allograft nephropathy following live donor kidney transplantation.