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Iranian ethnic groups in a global context. Relative sample locations with respect to the first two MDS components. Iranian ethnic groups in a global context (subset of "Old World" populations from the global 1000G data set); inlet zoomed view of the CIC and adjacent European populations. https://doi.org/10.1371/journal.pgen.1008385.g002
Source publication
Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, whil...
Citations
... km and is the second-largest country in the Middle East, followed by Saudi Arabia. According to the latest census data, Iran's population was 84,181,200 on January 9, 2021, composed of various ethnic, linguistic, dialect, and religious minorities who have been living in the country for a long time due to a high rate of inbreeding marriages that vary within each population [7][8][9]. Iran shares its northwest borders with Armenia and Azerbaijan, northeast with Turkmenistan, east with Afghanistan, southeast with Pakistan, and on its western borders with Turkey and Iraq. It also shares borders through the Caspian Sea in the north and the Persian Gulf and Gulf of Oman in the south [10]. ...
... Iran was one of the largest empires in history since the 6th century B.C. It took multitudinous forms of migration and invasion by countries from near and far, indicating the importance of studying Iran's population more than ever [8,9]. ...
The current study aimed to evaluate Y chromosome haplotypes obtained from 1353 unrelated Iranian males using the AmpFlSTRTM YfilerTM kit; 1353 out of the 1353 identified haplotypes were unique. The haplotype diversity (HD) and discriminating capacity (DC) values were 1.00000 and 0.997, respectively. Analysis of genetic distance was performed using molecular variance (AMOVA) and multidimensional scaling plots (MDS), revealing a statistically significant difference between the study population and previous data reported for other Iranian populations and other neighboring countries. The present findings are likely to be useful for forensic casework analyses and kinship investigations.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12864-024-10217-1.
... 23 Considering our results that suggested a significant role for urbanization in susceptibility to more frequent recurrence episodes, it is deducible that this high frequency of recurrent stone formers relative to all stone formers may be due to this factor. Moreover, a previous study has delineated the genetic differences among various Persian ethnicities, 24 which may be another possible explanation for the observed differences between different provinces, each of which are mostly inhabited by certain ethnic groups. ...
Background:
Prevention of urinary stone recurrence is the ultimate goal in urolithiasis patients. In this study, we aimed to investigate the national prevalence rate and possible determinants of increased urolithiasis recurrence risk in a nationwide study in Iran.
Methods:
All data regarding stone occurrence and recurrence episodes were extracted from the cross-sectional Iran National Stone Survey (INSS) study, and the possible determinants of recurrence were evaluated in the subset of 2913 patients who had a positive history of at least one episode of urolithiasis.
Results:
The national prevalence rate of recurrent urolithiasis was 2.6% (95% CI: 2.5, 2.8) in Iran. Moreover, the relative ratio of recurrent stone formers to all stone formers was 39.8% (95% CI: 38.0, 41.6). Our univariable truncated negative binomial regressions suggested that a positive history of urolithiasis in the patient's father (prevalence ratio [PR] [95% CI]=1.83 [1.39, 2.41], P<0.001), mother (PR [95% CI]=1.92 [1.39, 2.66], P<0.001) or brother (PR [95% CI]=1.32 [1.03, 1.69], P=0.026); and residence in urban areas (PR [95% CI]=1.27 [1.04, 1.55], P=0.016) were significant predictors of repetitive recurrence episodes. However, when incorporated into a multivariable truncated negative binomial regression model, the only significant predictors of more frequent recurrence episodes were a positive history in father (PR [95% CI]=1.66 [1.24, 2.22], P<0.001) and mother (PR [95% CI]=1.68 [1.20, 2.36], P=0.002); and urban residence (PR [95% CI]=1.24 [1.01, 1.51], P=0.031).
Conclusion:
Our results indicate that a positive family history of urolithiasis in mother and father and residence in urban areas are the significant predictors of recurrence risk in urolithiasis patients in Iran.
... Additionally, the findings of this research are likely to be helpful for further research on lipid traits in Iran. More importantly, this study unveiled the intuition and evidence needed to start profound genetic studies on lipid traits 55 . ...
Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28–9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.
... This database was established by whole-exome sequencing (WES) data of 800 healthy Iranian individuals from eight major Iranian populations, including Iranian Arabs, Azeris, Persians, Lurs, Baluchs, Persian Gulf Islanders, Kurds, and Turkmen. Iranome discovered more than 1,500,000 variants, more than 300,000 of which were novel [7,31]. The pathogenicity of these variants was investigated using six tools, including SIFT, Polyphen2, MutationTaster, MutationAssessor, FATHMM, and FATHMM MKL, as listed on the Iranome Website. ...
Background
Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Some of their subtypes are inherited in autosomal recessive patterns, so they are expected to be prevalent in populations like Iran, where consanguineous marriages are common. In the current work, a cohort of Iranian patients with overlapping phenotypes of the EDS/OI/CL and their mutation spectrum was defined. Based on this, in silico analysis was conducted to anticipate further probable genetic variations. Pathogenicity of EDS, OI, and CL variants in Iranian patients was evaluated using Web servers. A protein interaction network was created by String database and visualized using a Python-based library. The Iranome database was used to predict other genetic mutations in all reported genes of EDS, OI, and CL syndromes.
Results
In the EDS/OI/CL overlap phenotype, 32 variants in 18 genes have been involved. At least 59% of patients were from families with consanguineous marriages. Interaction analysis showed that COL1A1 , COL1A2 , CRTAP , LEPRE1 , PLOD1 , and ADAMTS2 have the most significant impact within the protein network of EDS/OI/CL overlap phenotype. Analyzing the Iranome database revealed 46 variants of EDS, OI, and CL genes potentially disease causing.
Conclusion
The overlapping phenotype of EDS, OI, and CL syndromes requires genetic testing (e.g., whole-exome sequencing) to reveal respective variants, which helps to diagnose more accurately and manage the disease more effectively. Particularly in populations with high rates of consanguineous marriages, such as Iran, genetic screening plays a crucial role in premarital and prenatal counseling to prevent the transmission of these rare connective tissue disorders.
... In addition, there are some evidences that confirm population differences in microRNA expression (18). Distinct genetic variation and heterogeneity of the Iranian and Afghan population has been detected (19,20). Identifying the relationship between miR-NA expressions in TB patients of Iranian and Afghan races may provide important information regarding TB pathogenesis, host susceptibility, and more effective control. ...
Background and Objectives
The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b).
Materials and Methods
A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs.
Results
Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f down-regulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348).
Conclusion
Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection.
... In addition, there are some evidences that confirm population differences in microRNA expression (18). Distinct genetic variation and heterogeneity of the Iranian and Afghan population has been detected (19,20). Identifying the relationship between miR-NA expressions in TB patients of Iranian and Afghan races may provide important information regarding TB pathogenesis, host susceptibility, and more effective control. ...
Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microR-NAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b). Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs. Results: Iranian (P<0.0001) and Afghan (P<0.0001) serum samples and Afghan (P<0.0001) sputum samples overexpressed miR-125a, whereas Iranian sputum samples showed downregulation (P=0.0039). In both Iranian (P<0.0001; P=0.0007) and Afghan (P<0.0001; P<0.0001) serum and sputum samples, miR-125b was overexpressed. Furthermore, miR-let-7f down-regulation was observed in serum and sputum samples (P<0.0001), whereas Iranian sputum samples had no statistically significant differences (P=0.348). Conclusion: Overexpression of miR-125a and miR-125b has been detected in Iranian and Afghan samples. In both races, miR-let-7f downregulation has been confirmed. Identification of miRNA profiles under different conditions opens the door to evaluating potential new biomarkers for diagnosis, disease monitoring, and therapeutic markers in TB infection.
... 14 With regard to heterogeneous ethnic groups in Iran, they show a high grade of genetic diversity. 15 The aim of this study was to investigate the spatial and time variations in lymphoma incidence as well as the children's (0-14 years) survival rate in Iran from 2005 to 2015. ...
Background
Childhood lymphoma is the second leading cause of cancer in children under 15 years of age in Iran. The aim of this study was to investigate the spatial and time variations in lymphoma incidence as well as the children’s survival time in Iran.
Method
This cross-sectional study was conducted using lymphoma cases (children under 14 years of age) from 2005 to 2015, and the data were obtained from the National Cancer Registry Center. The frequency, age-standardised incidence rate (ASIR), spatial clustering in national level and the survival rate (1 year and 5 years) using Kaplan-Meier method were evaluated. We used Spatial and Temporal Scan statistics software in order to detect statistically significant clusters in spatial analysis.
Results
A total number of 746 girls and 1610 boys were diagnosed with lymphoma during a 10-year period. ASIRs (per 100 000 people) for girls ranged from 0 in Ilam to 3.47 in Yasuj, and it ranged from 0.19 in Ilam to 5.91 in Yazd for boys from 2005 to 2015. Spatial analysis result showed a large statistically significant cluster (the most likely cluster) for both boys (relative risk (RR)=2.37) and girls (RR=2.49) located in the northwest of Iran. Fortunately, survival rate for both boys and girls was over 95.5%.
Conclusion
Lymphoma incidence rates had heterogeneous geographical distribution, and some significant clusters were identified which strengthens the role of possible aetiological factors, and further studies are needed to clarify this ambiguity. Fortunately, the survival rate of this cancer in Iran was good and it was similar to the high-income countries.
... In spite of the fact that mutations in these genes account for the majority of worldwide CMT cases, only one case in our studied samples carried such mutants (MFN2 in patient #2). This considerable difference between the results of our study and other published data is due to the distinct genetic variation of Iranian patients which is the result of consanguinity and numerous language adoptions (45). Totally, 9 pathogenic variants were identified in our study. ...
Background: More than 80 genes are involved in the pathogenesis of the most common single gene peripheral neuropathies denoted as Charcot-Marie-Tooth (CMT). Only a few studies have investigated the pathological molecular mechanisms of Iranian patients affected with CMT. The aim of this study is to identify the clinical manifestation, mutational spectrum and phenotypic correlation of a cohort of patients with Charcot-Marie-Tooth disease (CMT) in Iran. Methods: We conducted a comprehensive gene panel sequencing consisting of 80 genes in a cohort of 23 patients with CMT referred between January 2015 and March 2021. The recruited samples indicated almost an equal distribution of demyelinating and axonal types of CMT, with practically no difference between AD or AR patterns of inheritance. Results: Four novel mutations, including c.271C>T in LITAF and c.205+1delG in NDRG1, c.2455A>C in KIF1B and c.1728A>G in FIGF were detected in four patients affected with demyelinating CMT types (CMT1C and CMT4D), and characterized phenotypically. Conclusion: Our promising results unravel the complicated genetic architecture of Iranian CMT patients and help physicians and researchers achieve earlier diagnosis, better clinical management and recognizing high risk families. Further large-scale studies are needed to improve our understanding of CMT complex genetic architecture
... Several ethnicities with different dialects, languages, and religions form Iran's present-day population. Recent studies indicate that the Iranian population is highly heterogeneous yet genetically distinctive (Mehrjoo et al., 2019). This explains the heterogeneity of CFTR mutations observed in the present study. ...
Objectives: Cystic fibrosis (CF) is the most prevalent autosomal recessive disorder among Caucasians. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause this pathology. We, therefore, aimed to describe the CFTR mutations and their geographical distribution in Iran.
Method: The mutation spectrum for 87 families from all Iranian ethnicities was collected using ARMS PCR, Sanger sequencing, and MLPA.
Results: Mutations were identified in 95.8% of cases. This dataset revealed that the most frequent mutations in the Iranian population were F508del, c.1000C>T, c.1397C>G, c.1911delG, and c.1393-1G>A. In addition, we found weak evidence for Turkey being the possible geographical pathway for introducing CFTR mutations into Iran by mapping the frequency of CFTR mutations.
Conclusion: Our descriptive results will facilitate the genetic detection and prenatal diagnosis of cystic fibrosis within the Iranian population.
... Reports show that Iran has a considerable rate of opium use, especially methadone [22]. To the extent of our knowledge, CYP2B6 * 2 and * 3 have not been evaluated in Iranian populations, except for Southern Iran [23], which is previously reported to have a distinguished genetic pool from other Iranian populations [24]. ...
... As demonstrated in Tables 4 and 5, the CYP2B6 * 2 and * 3 allelic frequency is remarkably higher in the three main Iranian populations than in other ethnicities, even those in Southern Iran. It is believed that due to a considerable number of consanguineous marriages in Iran, autosomal recessive diseases highly manifest in this country; furthermore, it is said that Iranian allele frequency is noticeably diferent from those in Europeans, while Iranian Baluch seemed to have a tendency towards south Asians in allele frequency [23,24]. Besides, CYP2B is believed to have the most frequent interpersonal variety, which accounted for 20-250 times more than other Cytochrome P450 isoenzymes [40]. ...
Background:
Cytochrome P450 complex plays a key role in drug metabolism. CYP2B6 has an essential part in Cytochrome P450 complex metabolism. This study aims to determine the allelic distribution of CYP2B6∗2 and CYP2B6∗3 in three main Iranian ethnicities: Fars, Turk, and Kurd.
Methods:
The study was conducted on 174 unrelated healthy volunteers from three main Iranian ethnicities. After DNA extraction from peripheral blood samples, genotyping of CYP2B6∗2 and ∗3 was performed using tetra ARMS and ARMS PCR, respectively.
Results:
The average age of 174 cases was 40.69 ± 11.87 (mean ± SD) and 39.06 ± 11.63 (mean ± SD) for males and females. In the CYP2B6∗2 variant, the genotyping frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 8.7%, 86%, and 5.2%, respectively. The CYP2B6∗2 (c.64C > T) allele frequency was 48.2% (95% CI: (37.8-58.6)). In the CYP2B6∗3 variant, the frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 75.3%, 11%, and 13.6%, respectively. The CYP2B6∗3 (c.777C > A) allelic frequency was 19.1% (95% CI: (17.5-20.7)).
Conclusion:
Allelic distribution in three main Iranian ethnicities, i.e., Turk, Kurd, and Fars, is remarkably higher than that in other populations, even that in Southern Iran. High frequencies of CYP2B6∗2 and ∗3 in the Iranian population highly affect drug responsiveness. Understanding such variability could help to increase drug efficacy and reduce its toxicity.
