Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications

RESEARCH ARTICLE Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications Antonio Arnaiz-Villena1☯*, Jose Palacio-Grüber1☯, Ester Muñiz1, Cristina Campos1, Javier Alonso-Rubio1, Eduardo Gomez-Casado2, Shadallah Fareq Salih3, Manuel MartinVilla1, Rawand Al-Qadi3 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Immunology, University Complutense, School of Medicine, Madrid Regional Blood Center, Madrid, Spain, 2 Department of Inmunologı́a Animal, Instituto Nacional de Investigación y Tecnologı́a Agraria y Alimentaria (INIA), Autopista A6, Hipódromo, Madrid, Spain, 3 HLA Typing Department, Dohuk Specialized Laboratory Center, Dohuk, Iraq ☯ These authors contributed equally to this work. * Abstract OPEN ACCESS Citation: Arnaiz-Villena A, Palacio-Grüber J, Muñiz E, Campos C, Alonso-Rubio J, Gomez-Casado E, et al. (2017) Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications. PLoS ONE 12(1): e0169929. doi:10.1371/journal.pone.0169929 Editor: Tzen-Yuh Chiang, National Cheng Kung University, TAIWAN Received: September 6, 2016 Accepted: December 22, 2016 Published: January 23, 2017 Copyright: © 2017 Arnaiz-Villena et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper file. Funding: This work was supported in part by Grants from the Spanish Ministry of Health and Economy (PI11/00807 and PI14/01067), European FEDER funds and three different Mutua Madrileña Automovilista grants. Competing Interests: The authors have declared that no competing interests exist. Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52—DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11—DQB1*03, HLA DRB1*03— DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and also for Anthropology. It is discussed that one of the most ancient Kurd ancestor groups is in Hurrians (2,000 years BC). Introduction HLA is the most polymorphic genetic system described in man. It contains several linked loci which encode for cell surface proteins that have an important function in activating immune response after antigenic presentation. New allele variants are frequently being described (i.e.: 1,883 HLA-DRB1 alleles have been recorded by June 2016) [1]. HLA gene frequencies have both a large degree of variability among populations and a striking geographical correlation. These frequencies are useful to infer genetic background and ethnical constitution of modern human groups and also for inferring migrations of ancient ones [2]. In addition, certain combinations of contiguous alleles between HLA neighboring loci show a characteristic frequency due to the robust linkage disequilibrium among them or are distinctive in many extant populations [3]. PLOS ONE | DOI:10.1371/journal.pone.0169929 January 23, 2017 1 / 11 HLA of Kurds of Iraq, Iran and Caucasus Fig 1. Geographical location of Duhok in the Kurd Autonomous Province of Iraq. Erbil is province capital and is located about 170 km South East Duhok. (This Fig is similar but not identical to Fig 1 in Ref [13]; It has been included only for illustrative purposes). doi:10.1371/journal.pone.0169929.g001 Also, HLA allele frequencies are unique for studying the origins of relatively homogeneous groups, like the Kurd people living in Iraq. Other HLA gene characteristics are their link to disease and to different responses to drug treatments in patients according to different HLA alleles. Certain HLA alleles affect drug response to treatment in about sixteen different diseases including AIDS [4]. This is important for personalized drug treatment design (including ethnic groups with specific certain high allele frequencies), particularly if other already obtained Kurd HLA results are also included (from Georgia and Iran, in present study) and samples are further increased. On the other hand, Kurd people live in different countries in the Near East such as Syria, Armenia, Turkmenistan, Kazakhstan, Turkey, Iraq and Iran, the so called Kurdistan ("land of Kurds") (Fig 1, Table 1). Kurdistan is a region placed South Caucasus and North of ancient Mesopotamia. According to genetic studies (like HLA) in Turkish and Kurdish populations, a Anatolian-Mediterranean source for both populations was put forwards; it may be possible that Kurds are initially coming from ancient Hurrians, reviewed in [5,6]. Studies performed with mtDNA and Y-chr have also been done for Kurds, however there is no firm conclusion to infer that most Kurd people have originated either from Middle East and/or from Central Asia [7,8]. Most probably, Kurd people gene pool majority may be composed of an admixture of Table 1. Kurds population around the World [14,15]. Kurds Population Kurdistan Country Turkey Kurds Diaspora Number of inhabitants (x103) 12,000–22,500 Country Germany Iran 3,350–8,000 France Iraq 4,000–6,500 Israel Syria 2,000–2,500 37.5 Armenia Country Number of Inhabitants (x103) 800 Switzerland 35 150 Denmark 30 100–200 Jordan 30 Sweden 83.6 Austria 23 Belgium 80 Greece 22 70 USA 15.4 Kyrgyzstan 13.2 50 Canada 11.7 42.3 Finland 10.7 Georgia 14 Netherlands Azerbaijan 6.1 Russia UK Kazakhstan Total of Kurds: Number of Inhabitants (x103) 63.8 23,038,000–41,300,000 doi:10.1371/journal.pone.0169929.t001 PLOS ONE | DOI:10.1371/journal.pone.0169929 January 23, 2017 2 / 11 HLA of Kurds of Iraq, Iran and Caucasus Table 2. Populations used for this study. Reference Population N Reference Algerians Population 106 N [27] Lebanese 59 [21] Armenian 141 [19] Macedonians 178 [38] [31] Ashkenazi Jews 80 [28] Mansi 68 Baloch 100 [29] Moroccans 98 [39] Berbers (Souss) 98 [30] Moroccan Jews 113 [40] Buryat 25 [31] Negidal 35 [31] Chuvash 82 [32] Non-Ashkenazi Jews 80 [28] Cretans 144 [33] Palestinians 165 [41] Croatians (...truncated)