Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population
Zana Karimi Kurdistani1, Samaneh Saberi2, Yeganeh Talebkhan2, Akbar Oghalaie2, Maryam Esmaeili2, Nazanin Mohajerani2, Maryam Bababeik2, Parisa Hassanpour2, Shaghik Barani2, Ameneh Farjaddoost2, Fatemeh Ebrahimzadeh2, Jean Trejaut3, Marjan Mohammadi2
1 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran; Department of Molecular Genetics, Fars Science and Research Branch, Islamic Azad University, Shiraz, Iran
2 HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3 Mackay Memorial Hospital, Taipei, Iran
|Date of Submission||03-Dec-2014|
|Date of Acceptance||21-Jan-2015|
|Date of Web Publication||31-Jul-2015|
Dr. Marjan Mohammadi
HPGC Group, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, No. 69, Pasteur Blvd., Tehran 13164
Source of Support: None, Conflict of Interest: None
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 (H o ), expected heterozygosity (H e ), fixation index (F IS ), 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 (H o = 0.50 ± 0.24) and lowest (H o = 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.
Keywords: Allelic frequency, Arlequin, genetic diversity, polymorphism information content, single nucleotide polymorphisms
|How to cite this article:|
Kurdistani ZK, Saberi S, Talebkhan Y, Oghalaie A, Esmaeili M, Mohajerani N, Bababeik M, Hassanpour P, Barani S, Farjaddoost A, Ebrahimzadeh F, Trejaut J, Mohammadi M. Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population. Adv Biomed Res 2015;4:160
|How to cite this URL:|
Kurdistani ZK, Saberi S, Talebkhan Y, Oghalaie A, Esmaeili M, Mohajerani N, Bababeik M, Hassanpour P, Barani S, Farjaddoost A, Ebrahimzadeh F, Trejaut J, Mohammadi M. Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population. Adv Biomed Res [serial online] 2015 [cited 2023 Mar 22];4:160. Available from: https://www.advbiores.net/text.asp?2015/4/1/160/161809
| Introduction|| |
Iran (Persia) is a multi-ethnic country located in the Middle East. It is bordered on the north by the Caspian Sea and south by the Persian Gulf and the Gulf of Oman. Its population is comprised of genetically heterogeneous groups, but the exact ethnic composition of Iran remains loosely defined. Accordingly, Persians (Fars) constitute 61% of the population of Iran, followed by Turks (Azeri, 16%), Kurds (10%), Lurs (6%), Arabs (2%), Balochs (2%), Turkmens and Turkic tribes (2%), and other ethnicities (1%). The official language of Iran is Persian (Farsi), which is spoken by 53% of the population. Other languages include Turkish (18%), Kurdish (10%), Gilaki/Mazani (7%), Luri (6%), Balochi (2%), Arabic (2%) and others (2%). , Characterization of genetic profiles and analysis of differences between ethnic groups should provide a better understanding of their disparities and genetic susceptibility to disease. Such analyses are usually conducted using histocompatibility leukocyte antigens (HLAs),  cytokine gene polymorphisms  and other genetic markers such as microsatellites. ,,, Cytokines are key immune-modulatory molecules which regulate the activities of multiple target cells via binding to specific receptors and are involved in the pathogenesis of numerous diseases.  A number of functional polymorphisms within the regulatory regions of cytokine genes affect gene transcription, causing variations in their level of production. , The role of cytokine gene polymorphisms in screening for susceptibility to inflammatory diseases, transplant rejection, autoimmunity and various cancers has been vastly studied. ,,, Cytokine gene polymorphisms comprise of single nucleotide polymorphisms (SNPs), microsatellite polymorphisms, gene insertions and deletions. ,, Their distribution varies significantly among different ethnic groups, which in turn may contribute to the observed differences in ethnicity-dependent disease prevalence. ,,, The purpose of the current study was to investigate the genomic variation of a range of cytokine SNPs (IL-1β-511, IL-1β-31, IL-2-384, IL-4-590, IL-6-174, IL-8-251, IL-10-592, IL-10-819 and IL-10-1082). The studied cytokines were selected from the categories of pro- and anti-inflammatory cytokines, which are most associated with the development of various diseases, particularly cancers. In addition to the calculation of genetic diversity, similarities and differences among all tested groups and other worldwide populations was evaluated using MDS analysis.
| Materials and Methods|| |
In order to investigate cytokine functional SNP distribution, in the multi-ethnic population of Iran, we have assessed 415 unrelated healthy individuals from six major Iranian ethnic groups [Figure 1]. The study population comprised of 198 Fars, 139 Turk, 32 Gilaki, 23 Lur, 14 Kurd and 9 Mazani ethnic subjects. Geographical origins and ethnicities were determined by personal interview. Subjects were included whose parents were of the same ethnic groups. This study, including data and sample collection, was carried out following provision of written informed consents by the participants, according to protocols approved by the National Committee on Ethical Issues in Medical Research, Ministry of Health and Medical Education of Iran; Ref No. 315.
|Figure 1: Geographic distribution of Iranian ethnic groups. Colors indicate different ethnicities|
Click here to view
Venous blood (5 ml) was obtained from each subject for genetic studies. Genomic DNA was extracted from white blood cells using salting out extraction method.  The quality and quantity of DNA were determined by spectrophotometric measurement of absorbance at 260/280 nm, and the extracted DNAs were stored at −20°C for further processing.
Various PCR based methods including CTPP (confronting two-pair primers) and RFLP (restriction fragment length polymorphism) were used to identify SNPs in the following cytokine genes: 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 TNF-α (G-308A) [Table 1].
|Table 1: Primer sequences and methods used for detection of cytokine gene polymorphisms |
Click here to view
Briefly, the genomic DNA was amplified with specific primers [Table 1]. Each 20 μl of PCR reaction contained 50 ng DNA, 25 pM of each primers, 0.2 mM of each dNTPs, 1X PCR buffer, 1.5 mM MgCl 2 and 1 U Taq Polymerase (CinnaGen, Iran). PCR products were digested 3-16 h with suitable restriction enzymes at 37°C. PCR products and the resulting digested fragments were visualized by agarose gel electrophoresis. For each studied SNP, three randomly selected wild type and mutant samples were sequenced. Blinded cross-checking of PCRs, and random sequence analysis of PCR products validated the genotyping results.
Allelic and genotypic frequencies for each SNP were estimated by PyPop software.  Departures from Hardy-Weinberg equilibrium (HWE; P < 0.05) was calculated by the method of Guo and Thompson using the Arlequin implementation  accessed via PyPop.  A Chi-squared test was performed to evaluate ethnicity-specific differences in pairwise allelic frequencies using SAS software.  The population genetic indices namely; observed heterozygosity (H o ), expected heterozygosity (H e ), fixation index (F IS ), and the effective number of alleles (Ne ) were derived using Popgene 32 software version 1.32.  The polymorphism information content (PIC) was calculated using the method described by Botstein et al.
Multidimensional scaling was constructed using Reynold's genetic distance obtained from the frequencies of cytokine gene polymorphism, using Microsoft® Excel 2000/XLSTAT-Pro (Version 7.2, 2003, Addinsoft, Inc., Brooklyn, NY, USA). Additional data that were added to the MDS database included other Iranian populations (Tehran, Yazd, Sistani and Baloch)  and non-Iranians ,
| Results|| |
Allelic and genotypic frequencies for each locus of every ethnic group are presented in [Table 2]. Most loci were in HWE with the exception of the following loci: IL-4-590, IL-8-251, and IL-10-819 in Fars, and IL-4-590, IL-6-174, IL-10-1082 and TNF-α-308 in Turks.
|Table 2: Allelic and genotypic frequencies of cytokine gene polymorphisms in different ethnic groups |
Click here to view
Pairwise assessment of allelic frequencies, for the 10 SNPs in our six different ethnic groups, detected statistically significant differences exclusively at the IL-4-590 locus in Gilakis versus Kurds and Lurs (P = 0.028 and P = 0.022, respectively) [Table 3]. A poorly significant difference was also observed in Gilakis versus Fars and Turk for this locus (P = 0.082 and P = 0.071, respectively). Gilakis also demonstrated this trend in other loci, namely for IL-6-174, IL-10-819 versus Fars (P = 0.064) and Kurds (P = 0.072), respectively. In addition to Gilakis, Mazanis also manifested borderline statistical differences with Kurds and Turks for IL-10-1082 (P = 0.073 and P = 0.056, respectively) [Table 3].
|Table 3: Statistical differences between allelic frequencies of different loci among six Iranian ethnic groups |
Click here to view
The values obtained for genetic diversity, namely H o , H e , Ne PIC, and F IS are presented in [Table 4]. The H o in all ethnic groups at the IL-4-590 locus was higher than expected (H o > H e , negative F IS value). The widest range of Ne values was observed in Kurds ranging from 1.08 (TNF-α-308) to 2.0 (IL-2-384). In contrast, a narrower range was observed in Lurs, ranging from 1.26 (TNF-α-308) to 1.99 (IL-1β-511 and IL-10-1082). According to the criteria of Botstein et al.,  our population is characterized by a medium genetic diversity at every locus (0.25 < PIC < 0.50) [Table 4]. Mazanis showed excess heterozygosity (negative F IS value) at all loci with the exception of the IL-10 (-592, -819, -1082). On the contrary, Gilakis showed low heterozygosity (positive F IS value) at all loci, with the exception of IL-10-819 and IL-4-590, IL-2-384.
|Table 4: Calculated genetic diversity values for the different Iranian ethnicities |
Click here to view
The mean values of H o , H e and Ne for each ethnic group are shown in [Table 5]. Mazanis displayed the highest mean H o (0.50 ± 0.23), whereas Gilakis possessed the lowest (0.33 ± 0.15). The highest and lowest mean number of effective alleles (Ne ) were seen in Lurs (Ne = 1.83 ± 0.22) and Mazanis (Ne = 1.64 ± 0.27), respectively.
|Table 5: Mean values of observed and expected heterozygosities and number of effective alleles at all loci |
Click here to view
The MDS plot of our data set [[Figure 2]a, stress 0.149] was obtained using all cytokine gene polymorphisms as shown in [Table 2]. This plot shows two outlier Iranian ethnic groups; the Kurds and Mazanis, at the top and bottom of the MDS plot, respectively, which were clearly separated from a tight cluster comprising the remaining ethnic groups in the center of the plot. The MDS plot of the combination of all studied Iranian populations with those of other countries was constructed using cytokine gene polymorphisms tested in all groups, (IL-1β-511, IL-2-384, IL-4-590, IL-10-1082,-819,-592 and TNF-α-308) [[Figure 2]b; stress = 0.096]. This MDS plot identified four distinct clusters. The European cluster included Brazil and India, to the left, which were characterized by higher frequency of IL-1β-511C, IL-10-1082G and IL-10-592A (data not shown). The Iranian population cluster, to the right, identified the Mazani ethnic group as an outlier and overlapped the HapMap-reported European data. The East Asian populations segregated into two separate clusters with Taiwan and Korea (characterized by higher occurrence of IL-4-590T and IL-10-819T; data not shown), and Japan and China, which unexpectedly shared a similar overall frequency profile with Sub-Sahara Africans.
|Figure 2: The multidimensional scaling (MDS) plot of cytokine gene polymorphisms in (a) Iranian populations for IL-1β (-511), IL-4 (-590), IL-6 (-174), IL-10 (-1082), IL-10 (-819), IL-10 (-592) and TNF-α (-308) loci; (b) in comparison with other populations (European, East Asia, and sub-Sahara African) for IL-1β (-511), IL-2 (-384), IL-4 (-590), IL-10 (-1082), IL-10 (-819, -592) and TNF-α (-308) loci|
Click here to view
| Discussion|| |
Variations in cytokine gene polymorphisms, associated with ethnic differences, may reflect susceptibility to various diseases and has also been used as a tool for anthropological studies. ,,,,,, Such studies are of paramount importance for better diagnosis, prognosis and management of disease. ,,
In this study, we have evaluated the distribution of functional SNPs of ten different pro- and anti-inflammatory cytokines in six major Iranian ethnic groups. HWE analysis identified deviations in IL-4-590, IL-8-251, IL-10-1082 and TNF-α-308 loci, which may be a consequence of several reasons, namely; technical complications (sample mishandling, DNA contamination, and typing error), admixture of ethnicities, natural selection, and inbreeding. Most populations in our dataset were in HWE and supported previous findings. ,,, Fars and Turk ethnicities, however, showed HWE deviation in certain loci. The accuracy of our technical procedures were confirmed by random sequencing and blinded cross-checks. Our sampling was performed in Tehran and subjects whose parents were of different ethnicities were excluded. Nonetheless, the observed deviations could be either population-specific,  or a consequence of high level of migration of other ethnicities (nonFars) toward Tehran (Fars) in the recent decades.  The latter could have caused admixture of ethnicities at the level of grand parental generations.
Allelic frequency distribution suggested a relatively high degree of homogeneity amongst our different ethnic populations. The most noticeable and significant differences were observed for the IL-4-590C allele frequency in Gilakis (as the highest; 88%) versus Kurds and Lurs (as the lowest; 66-69%). Taking into account that IL-4-590C is associated with lower levels of immunoglobulin E production,  we can speculate that higher rates of Helminths infection in the north of Iran, and Gilan in particular  may have caused a pressure over many generations to select for genetically-based high-IL-4 producers and hence for those better equipped for IgE-mediated anti-parasitic responses. ,
On another note, significant differences in allele frequencies between different ethnic groups are also caused by unequal allele frequencies in the ancestral populations.  With this perspective in mind, it is believed that Gilakis have originated from the South Caucasus and significantly differ from Kurds and Lurs who have distinctive origins. 
Our observed Ne and PIC values for TNF-α-308 indicated a low level of genetic diversity amongst Fars, Kurds and Mazanis ethnicities. In addition, the F IS value observed for the examined locus suggests a condition of equilibrium in the population which is supported by the χ2 test results used to verify the HWE. Deviation of genotypic frequencies F IS and H o in Mazani and Fars ethnic groups indicated high genetic variation. Mazani and Gilaki, as mentioned above, originated from the Caucasus and now live in the north of Iran.  Intriguingly, and calling for further analysis, is the highest and the lowest gene heterozygosity seen in Mazanis and Gilakis, respectively.
Ultimately, we used MDS to visualize similarities within and between Iranian ethnic groups and with those of other populations. According to MDS analysis all our ethnic groups, except for the Kurds and Mazanis, clustered together. This observation was expected for the Kurds, as they are believed to have remained isolated over the years.  On the other hand, Mazanis may have avoided admixture of populations following Russian invasion of north of Iran in the early 18 th century  and have remained secluded to the present days.
The three clusters observed in [Figure 2]b are in good agreement with a long history of migration and separation. While the distribution of cytokine alleles clearly distinguishes Iranian groups from most European groups, it maintains a close genetic affinity with this group. Accordingly, it has been suggested that the Iranians might have relatively close evolutionary history with people of Russia rather than East Asian populations.  Despite the clear clustering of all Asian groups from other groups, the position of the Sub-Saharan Africans among Chinese and Japanese populations remains intriguing.
In general, our data, based on cytokine gene polymorphism, mostly indicate genetic homogeneity of the Iranian population, despite its multi-ethnic composition. The allelic and genotypic frequencies of Iranian populations present closer affinity to Europeans rather than to Asians groups. The few mentioned disparities in cytokine allele frequencies for some of our ethnic populations, however, call for careful selection of cases and controls and subsequent adjustments when performing disease association studies, to avoid misrepresentations.
| Acknowledgments|| |
This study was supported by a technical assistance grant (IRN-072), which was co-funded by the Islamic Development Bank, Saudi Arabia and Pasteur Institute of Iran.
| References|| |
Available from: https://www.cia.gov/library/publications/the-world-factbook/.
Trajkov D, Arsov T, Petlichkovski A, Strezova A, Efinska-Mladenovska O, Gogusev J, et al.
Distribution of the 22 cytokine gene polymorphisms in healthy Macedonian population. Bratisl Lek Listy 2009;110:7-17.
Chen YH, Huang YS, Chien WH, Chen CH. Association analysis of the major histocompatibility complex, class II, DQ ß1 gene, HLA-DQB1, with narcolepsy in Han Chinese patients from Taiwan. Sleep Med 2013;14:1393-7.
Vu D, Sakharkar P, Shah T, Naraghi R, Yasir Q, Hutchinson I, et al.
Association of interferon gamma gene polymorphisms with BK virus infection among Hispanic renal allograft recipients. Transplantation 2014;97:660-7.
Ma J, Wang YB, Li K, Wang JW. Polymorphisms of 21 short tandem repeat loci of Salar minority ethnic group in Qinghai Province. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2013;35:535-41.
Laguila Visentainer JE, Lieber SR, Lopes Persoli LB, Dutra Marques SB, Vigorito AC, Penteado Aranha FJ, et al.
Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population. Cytokine 2005;32:171-7.
Reynard MP, Turner D, Navarrete CV. Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet 2000;27:241-9.
Uboldi de Capei MU, Dametto E, Fasano ME, Rendine S, Curtoni ES. Genotyping for cytokine polymorphisms: Allele frequencies in the Italian population. Eur J Immunogenet 2003;30:5-10.
Qaddourah RH, Magdoud K, Saldanha FL, Mahmood N, Mustafa FE, Mahjoub T, et al.
IL-10 gene promoter and intron polymorphisms and changes in IL-10 secretion in women with idiopathic recurrent miscarriage. Hum Reprod 2014;29:1025-34.
Trejaut JA, Tsai ZU, Lee HL, Chen ZX, Lin M. Cytokine gene polymorphisms in Taiwan. Tissue Antigens 2004;64:492-9.
Golovleva I, Saha N, Beckman L. Ethnic differences in interferon-alpha allele frequencies. Hum Hered 1997;47:185-8.
Scarel-Caminaga RM, Trevilatto PC, Souza AP, Brito RB, Line SR. Frequencies of the -330 (T --> G) IL-2 and -590 (T --> C) IL-4 gene polymorphisms in a population from south-eastern Brazil. Eur J Immunogenet 2002;29:293-6.
Hoffmann SC, Stanley EM, Cox ED, DiMercurio BS, Koziol DE, Harlan DM, et al.
Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant 2002;2:560-7.
Gao L, Zhu X, Li Z, Li L, Wang T, Hu H, et al.
Association between a functional insertion/deletion polymorphism in IL1A gene and risk of papillary thyroid carcinoma. Tumour Biol 2014;35:3861-5.
Wren C, Campbell RW. The response of paediatric arrhythmias to intravenous and oral flecainide. Br Heart J 1987;57:171-5.
Oh JH, Yang CS, Noh YK, Kweon YM, Jung SS, Son JW, et al.
Polymorphisms of interleukin-10 and tumour necrosis factor-alpha genes are associated with newly diagnosed and recurrent pulmonary tuberculosis. Respirology 2007;12:594-8.
Reviron D, Dussol B, Andre M, Brunet P, Mercier P, Berland Y. TNF-alpha and IL-6 gene polymorphism and rejection in kidney transplantation recipients. Transplant Proc 2001;33:350-1.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
Lancaster AK, Single RM, Solberg OD, Nelson MP, Thomson G. PyPop update - A software pipeline for large-scale multilocus population genomics. Tissue Antigens 2007;69 Suppl 1:192-7.
Schneider S, Roessli D, Excoffier L. Arlequin: A software for population genetics data analysis, version 2.000. Switzerland: Genetics and Biometry Laboratory, Department of Anthropology, University of Geneva; 2000.
Hatcher L. A Step-by-Step Approach to Using the SAS System for Factor Analysis and Structural Equation Modeling. SAS Institute; 1994.
Yeh FC, Yang R, Boyle TJ, Ye Z, Xiyan JM. PopGene32, Microsoft Windows-based freeware for population genetic analysis, version 1.32. Edmonton, Alberta, Canada: Molecular Biology and Biotechnology Centre, University of Alberta; 2000.
Botstein D, White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 1980;32:314-31.
Amirzargar AA, Naroueynejad M, Khosravi F, Dianat SS, Rezaei N, Mytilineos J, et al.
Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw 2008;19:104-12.
Thorisson GA, Smith AV, Krishnan L, Stein LD. The International HapMap Project Web site. Genome Res 2005;15:1592-3.
Gonzalez-Galarza FF, Christmas S, Middleton D, Jones AR. Allele frequency net: A database and online repository for immune gene frequencies in worldwide populations. Nucleic Acids Res 2011;39:D913-9.
He J, Deng L, Na F, Xue J, Gao H, Lu Y. The association between TGF-ß1 polymorphisms and radiation pneumonia in lung cancer patients treated with definitive radiotherapy: A meta-analysis. PLoS One 2014;9:e91100.
Costeas PA, Koumas L, Koumouli A, Kyriakou-Giantsiou A, Papaloizou A. Cytokine polymorphism frequencies in the Greek Cypriot population. Eur J Immunogenet 2003;30:341-3.
Chinnaswamy S, Das K, Bairagya BB, Bhattacharyya C, Shalimar, Duseja A, et al.
Association of IL28B single nucleotide polymorphism rs8099917 with response to treatment in genotype 3 HCV-infected patients from India. Trop Gastroenterol 2014;35:96-102.
Shi Q, Wang XS, Li G, Shah ND, Orlowski RZ, Williams LA, et al.
Racial/ethnic disparities in inflammatory gene single-nucleotide polymorphisms as predictors of a high risk for symptom burden in patients with multiple myeloma 1 year after diagnosis. Cancer 2014; 1-9
Kaur G, Rapthap CC, Kumar N, Kumar S, Neolia S, Mehra NK. Frequency distribution of cytokine gene polymorphisms in the healthy North Indian population. Tissue Antigens 2007;69:113-20.
Trajkov D, Petlichkovski A, Efinska-Mladenovska O, Hristomanova S, Djulejic E, Kirijas M, et al.
Distribution of 22 cytokine gene polymorphisms in Roma from the Republic of Macedonia. Iran J Allergy Asthma Immunol 2012;11:282-93.
Bagheri M, Abdi-Rad I, Omrani D, Khalkhali HR. Heterogeneity of cytokine single-nucleotide polymorphisms among the Iranian and in the other East-South Asian populations. Transfus Med 2006;16:192-9.
Chaleshtori MH, Rad LH, Dolati M, Sasanfar R, Hoseinipour A, Zohour MM, et al
. Frequencies of mutations in the connexin 26 gene (GJB2) in two populations of Iran (Tehran and Tabriz). Iran J Public Health 2005;34:1-7
Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, et al.
Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 1995;25 Suppl 2:74-8.
Rokni MB. The present status of human helminthic diseases in Iran. Ann Trop Med Parasitol 2008;102:283-95.
Rockman MV, Hahn MW, Soranzo N, Goldstein DB, Wray GA. Positive selection on a human-specific transcription factor binding site regulating IL4 expression. Curr Biol 2003;13:2118-23.
Le Souëf PN, Candelaria P, Goldblatt J. Evolution and respiratory genetics. Eur Respir J 2006;28:1258-63.
Mattei J, Parnell LD, Lai CQ, Garcia-Bailo B, Adiconis X, Shen J, et al.
Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites. BMC Genet 2009;10:45.
Grugni V, Battaglia V, Hooshiar Kashani B, Parolo S, Al-Zahery N, Achilli A, et al.
Ancient migratory events in the Middle East: New clues from the Y-chromosome variation of modern Iranians. PLoS One 2012;7:e41252.
Langaroudi RR. GÎLÂN vi. History in the 18 th
Century 2001. Available from: http://www.iranicaonline.org/articles/gilan-vi.
Fazeli Z, Vallian S. Molecular phylogenetic study of the Iranians based on polymorphic markers. Gene 2013;512:123-6.
Hamajima N, Matsuo K, Saito T, Tajima K, Okuma K, Yamao K, et al.
Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori
infection. Jpn J Cancer Res 2001;92:383-9.
Noguchi E, Shibasaki M, Arinami T, Takeda K, Yokouchi Y, Kawashima T, et al.
Association of asthma and the interleukin-4 promoter gene in Japanese. Clin Exp Allergy 1998;28:449-53.
de Jong BA, Westendorp RG, Bakker AM, Huizinga TW. Polymorphisms in or near tumour necrosis factor (TNF)-gene do not determine levels of endotoxin-induced TNF production. Genes Immun 2002;3:25-9.
Kuroda S, Puri P. Lack of association of IL8 gene polymorphisms with familial vesico-ureteral reflux. Pediatr Surg Int 2007;23:441-5.
Koss K, Fanning GC, Welsh KI, Jewell DP. Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3' mismatches in forward and reverse primers. Genes Immun 2000;1:321-4.
Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol 1999;7:127-8.
Karhukorpi J, Laitinen T, Karttunen R, Tiilikainen AS. The functionally important IL-10 promoter polymorphism (-1082G-->A) is not a major genetic regulator in recurrent spontaneous abortions. Mol Hum Reprod 2001;7:201-3.
Shih CM, Lee YL, Chiou HL, Hsu WF, Chen WE, Chou MC, et al.
The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer 2005;50:291-7.
Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, et al.
Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori
infection. Gut 2004;53:1082-9.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|This article has been cited by|
||Polymorphism of the IL-10 gene in Azeri population of Iran
| ||Mohammad Asgharzadeh, Zahra Taghinejad, Vahid Asgharzadeh, Bahareh Mehramouz, Jalil Rashedi, Behroz Mahdavipoor, Mahya Pourostadi, Ali Vegari, Ali Safarzad Vishkaei, Sepehr Taghizadeh, Hossein Samadi Kafil |
| ||Egyptian Journal of Medical Human Genetics. 2022; 23(1) |
|[Pubmed] | [DOI]|
||Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega, Jalisco, Mexico
| ||HAZAEL RAMIRO CEJA-GALVEZ, ERANDIS DHENI TORRES-S?CHEZ, JUAN HERIBERTO TORRES-JASSO, EMMANUEL REYESURIBE, JOEL SALAZAR-FLORES |
| ||BIOCELL. 2021; 45(5): 1241 |
|[Pubmed] | [DOI]|
||Genetic Polymorphism of Tumor Necrosis Factor-Alpha, Interferon-Gamma and Interleukin-10 and Association With Risk of Mycobacterium Tuberculosis Infection
| ||Gashaw Adane, Mulualem Lemma, Demeke Geremew, Tekeba Sisay, Mekibib Kassa Tessema, Debasu Damtie, Birhanu Ayelign |
| ||Journal of Evidence-Based Integrative Medicine. 2021; 26: 2515690X21 |
|[Pubmed] | [DOI]|