Stayoussef et al. (2009) investigated the association of HLA class II (DRB1 and DQB1) haplotypes with type 1 diabetes (T1D) in Bahrain (Arabian Peninsula), Lebanon (eastern Mediterranean), and Tunisia (North Africa), in particular with regard to the identification of the specific haplotypes that confer susceptibility to and protection from T1D in each community. Study subjects comprised unrelated Arab subjects from Bahrain (126 patients, 126 controls), Lebanon (78 patients, 111 controls), and Tunisia (50 patients, 50 controls). DRB1*030101-DQB1*0201 was found to be a locus that conferred susceptibility in three populations, while DRB1*040101-DQB1*0302 was found to be a locus that conferred susceptibility only in Tunisians and Bahrainis. The DRB1*100101-DQB1*050101 (Bahrainis) and DRB1*150101-DQB1*060101 (Lebanese) loci were found to be largely protective. Stayoussef et al. (2009) concluded that the contribution of HLA to T1D must be evaluated with regard to ethnic background.

Mahdi et al. (2009) investigated the association of human leukocyte antigens (HLA) class II alleles and haplotypes with the pathogenesis of acute chest syndrome (ACS) in a population of Bahraini sickle cell anemia (SCA) patients. The population study comprised 186 SCA patients, of whom 58 had documented ACS (new pulmonary infiltrate, fever, and other associated clinical events) and 128 with a negative history of ACS, serving as controls. Of the DRB1* and DQB1* alleles analyzed, only DRB1*130101 (Pc < 0.001) was found to be positively associated with ACS. DRB1*130101-DQB1*060101 haplotype was found to be more prevalent among ACS patients (P = 0.018), thus conferring disease susceptibility. Mahdi et al. (2009) concluded that specific HLA alleles and haplotypes may influence ACS risk in SCA patients, and specific HLA genotypes may be useful markers for identifying high-risk SCA ACS patients.

Gibert et al. (2006) compared the spectrum of HLA-DRB1 alleles in the Comorian population, and compared it to known polymorphisms in this gene from Sub-Saharan African and Indian Oceanian populations to determine the genetic relationships between them. A total of 117 unrelated Comorian adults were typed for their HLA-DRB1 alleles using PCR and SSOP (sequence specific oligoneucleotide hybridization with ddUTP-labelled probes). Interestingly, particularly high frequencies were not noticed for any of the alleles, specifying the lack of a strong genetic drift due to isolation in the Comorian population. However, the observed heterozygosity was relatively high, indicating an excess of heterozygotes. Gibert et al. (2006) surmised that this could be an effect of balancing selection, but could also be due to admixture. The most common alleles detected in this population were HLA-DRB1*11 (24.6%), DRB1*13 (15.1%), and DRB1*15 (15%). Interestingly, these alleles are also the most common ones in the Gabonese, Congolese, Egyptian, and Greek populations. Other alleles detected included DRB1*01, DRB1*03 (found in Middle Eastern and African populations), DRB1*07, and DRB1*12 (present in South East Asian populations). Alleles found to be rare in the Comorian population included DRB1*08, DRB1*09, and DRB1*14 (all found prominently in Asian populations), DRB1*16 (found in South Eastern Europe, including Greek populations), and DRB1*04, and DRB1*07 (rarely found in North-East African and the Middle Eastern populations). Comparing the genetic polymorphisms of Comorians to polymorphism frequencies of other populations, the Comorians were found to be genetically closest to the Congolese, followed by Iranians, Egyptians, Gabonese, and Jews. Thus, the Comorian population is thought to be intermediate between the North East African, the Middle Eastern, and Sub Saharan populations.

Bakr and El-Chenawy (1998) investigated the association between steroid-sensitive nephrotic syndrome (SSNS) of children and several HLA-DQ and DR alleles using DNA polymerase chain-reverse hybridization. Twenty-seven Egyptian children (16 males and 11 females, aged 3-8 years) with SSNS constituted the study population, of whom 20 were infrequent relapsers, and seven were frequent relapsers with or without steroid dependency. Seven patients (4 males and 3 females, aged 6-14 years) with steroid-resistant nephrotic syndrome (SRNS) were also studied. The results were compared with 121 healthy subjects for HLA-DRB1 and 59 subjects for DQB1 alleles. Bakr and El-Chenawy (1998) found that patients with SSNS do not have significantly higher frequencies of DRB1*0101, *0102, and *0103 alleles than controls. However, when these subtypes were grouped together, the DRB1*01 frequency was found to be significantly higher (44.4% in patients vs. 3.3% in controls) and its relative risk was significantly high. DQB1*0601 was also found in high frequency among SSNS patients in this study. Bakr and El-Chenawy (1998) did not detect linkage disequilibrium between DQB1*0601 and DRB1*01, either in the patients or controls, denoting the independent role of each locus in the pathogenesis of the disease. The frequency of DRB1*11 alleles was found to be low in SSNS patients (3.75% in patients vs. 32.2% in controls), but was found to be not significant when P was corrected. Bakr and El-Chenawy (1998) did not find any significant differences in the distribution of DRB1* alleles between SRNS patients and controls. Bakr and El-Chenawy (1998) concluded that DQB1*0601 and DRB1*01 or closely associated unknown genes confer susceptibility to SSNS in Egyptian children. Bakr and El-Chenawy (1998) recommended that further studies are needed on a larger numbers of patients to confirm these results. In 2005, Bakr and El-Chenawi studied DRB1 alleles in 34 Egyptian children with childhood primary nephritic syndrome (PNS). Of the patient group, 20 were frequent relapsers/steroid-dependent (FR/SD; 12 males and 8 females, aged 9.2+/-2.4 years) and 14 were steroid-resistant (SR) children with minimal change nephritic syndrome (MCNS; 10 males and 4 females, aged 10.2+/-3.6 years). The results were compared with 121 unrelated healthy controls from the northern part of Egypt.

Bakr and El-Chenawi (2005) found that the DRB1*07011 allele frequency is significantly higher among patients than controls (78.9% vs. 16%, Pc<0.001). The etiological fraction (EF) was found to be high at 0.75. Furthermore, the relative risk (RR) was found to be high at 20.1 (confidence interval (CI) =6.0-66.7) and significant. Similarly, patients with steroid-resistant MCNS were found to have a higher frequency of the DRB1*07011 allele than controls (64.3% vs. 16.5%, Pc<0.001). The EF was found to be high at 0.57 (RR=9.6, CI 2.9-31.7). In the whole group of patients the frequency of DRBI*11 alleles was found to be low compared with controls (11.4% vs. 32.2%, P =0.02), but was not significant when P value was corrected. Bakr and El-Chenawi (2005) concluded that the DRBI*07011 allele confers susceptibility to an FR and SD or SR course of childhood MCNS. Bakr and El-Chenawi (2005) suggested that these patterns of the disease seem to have the same immunogenetic components.

Sánchez-Velasco et al. (2001) studied major histocompatibility complex (MHC) class I and class II alleles in 100 unrelated adult Jordanians of both sexes from the capital Amman and in 46 individuals from the Jordan valley. Sánchez-Velasco et al. (2001) identified 26 different alleles in the Jordanian population for the DRB1 locus; DRB1*0704 (0.2552), DRB1*0401 (0.1965), and DRB1*1501 (0.0896) being the most frequent. Besides that, Sánchez-Velasco et al. (2001) noted that three-loci haplotype heterogeneity was common and identified 38 HLA class II haplotypes in this population. The most frequent 3-loci haplotype observed in this population was DRB1*0401-DQA1*0301-DQB1*0302 (0.1793) followed by DRB1*0704-DQA1*0201-DQB1*0202 (0.1552). In addition, 220 different five-loci haplotypes with several unusual allelic combinations were observed, although many of them are pan-European haplotypes. The most frequent five-loci haplotype was found to be the A30-B7-DRB1*03-DQA1*0501-DQB1*0201 (0.0138). Since several Jordanian haplotypes were not found in the literature available at the time, Sánchez-Velasco et al. (2001) suggested that the specific Jordanian haplotypes are: A31-B7-DRB1*04/07-DQA1*0301/0201-DQB1*0302/0202 (0.0103) and A1-B7-DRB1*07-DQA1*0201-DQB1*0202, A2-B7-DRB1*04-DQA1*0301-DQB1*0302, and A11-B7-DRB1*07-DQA1*0201-DQB1*0201 haplotypes but at lower frequencies (0.007). Sánchez-Velasco et al. (2001) made a tree analysis of HLA class I and class II alleles for several Caucasian populations and calculated individual genetic distances. Haplotype frequencies, genetic distances, and dendrograms did not reveal great differences as compared with those in other Mediterranean countries and Western Europeans populations. These results led Sánchez-Velasco et al. (2001) to suggest that both HLA class I and class II polymorphisms (but especially the former) of the Jordanian population demonstrate considerable heterogeneity, which reflects ancient and recent admixture with neighboring populations, and important human migratory trends throughout the history.

Haider et al. (1999) performed typing of HLA-DR alleles in 212 normal healthy. DR3 was found to be the most common type in the Kuwaiti general population (28%) and DRB1*0301 was detected in 41% of the individuals with DR3 specificity.

Later, Haider et al. (2000) established the frequency of HLA DRB1 alleles in a cohort of 194 unrelated Kuwaiti Arabs. The cohort comprised of 80 schizophrenia patients (60 males, 20 females, and age range of 19-69) and 114 ethnically matched healthy controls (71 males, 43 females, and mean age of 45.6 years) with no family history of mental illness, with a sum of 12 classified DRB1 alleles. The frequency of DRB1*04 and DRB1*13 alleles were found to have a statistically significant distinction among schizophrenia patients (14% and 18%, respectively) and controls (7% and 9%, respectively), P = 0.028, 0.015, respectively. The frequency of DRB1*03, DRB1*07, and DRB1*16 alleles was observed to be higher in controls than schizophrenia patients, whereas the frequency of DRB1*01, DRB1*08, DRB1*10, DRB1*11, and DRB1*15 alleles appeared to be nearly identical among controls and schizophrenia patients. DRB1*12 was found in one schizophrenia patient and none in the control group. Haider et al. (2000) displayed that the remaining alleles did not demonstrate any statistically significant variation amongst the two groups and demonstrated the high incidence of DRB1*13 allele among Kuwaiti Arabs with schizophrenia compared to controls.

Al-Eisa et al (2000) studied the effect of HLA-DRB1 alleles on the clinical presentation of Kuwaiti Arab children with idiopathic nephrotic syndrome of childhood (INS). A total of 61 Kuwaiti children with INS constituted the study population, of whom 49 patients were steroid sensitive with or without steroid dependency, while 12 were steroid resistant. The control group consisted of 59 children who were admitted with minor illnesses and had no proteinuria on urine analysis (30 females and 29 males, aged ranged from 6 months to 12 years). The DRB1*0701(DR7) was found to be the most prevalent DR allele, found in 41/61 patients (67%) compared with 10/59 healthy controls (17%; p<0.001). Eleven of the 41 DRB1*0701(DR7)-positive patients were found to homozygous (27%) while 30/41 (73%) were found to be heterozygous. The DR3(*0301-0308) allele was found to be the second most common, found in 25% of patients compared with 26% of controls (not significant). The frequency of the combined DR7-DR3 alleles was reported to be 39% (16/41) in patients with INS compared with 6% (4/59) in controls (p<0.01). No significant difference was found between DRB1*0701(DR7)-positive and DRB1*0701-negative patients in terms of steroid sensitivity, steroid dependency, or steroid resistance. Nevertheless, the former group had a significantly lower mean age of onset (35 months vs 53 months) and a shorter remission period following treatment with cyclophosphamide or chlorambucil (8 months vs 29 months). Al-Eisa et al (2000) concluded that the DRB 1*0701 allele plays a role in predisposing Kuwaiti Arab children with idiopathic nephrotic syndrome to a more prolonged course of the disease in terms of earlier age of onset and a shorter remission after a course of alkylating agents.

Alsaeid et al. (2002) determined the prevalence of the HLA DR alleles in Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to that in 212 ethnically matched normal healthy. The patient group consisted of 69 children, of whom 52 were found to be oligoarticular and 17 were found to be RF-negative polyarticular. Of these patients, 15 were found to be positive for antinuclear antibody (21.7%) and six were diagnosed with iridocyclitis (8.7%). A very high incidence of DR3 was detected in JRA patients compared to the controls (P < 0.0001, RR = 2.235). The high incidence of HLA-DR3 in JRA patients was accounted for mainly by an excess of DRB1*0307 (P < 0.05, RR = 3.072) and DRB1*0308 (P < 0.009, RR = 2.663) compared to the controls. Moreover, DR3 was found to be more prevalent when patients with ANA-positive JRA were analyzed separately; 73% compared to 58% for the whole JRA patient group. The frequency of DR1 was also found to be higher in the JRA group compared to controls (P = 0.019, RR = 3.585). Although the incidence of some alleles was found higher in the control group (DR13 and DR7), none reached a statistically significant level. All the patients with iridocyclitis were found to have either a DR1 or DR3 allele, except for one child. The frequency of DRB1*03 was found to be much higher in the polyarticular subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the controls. Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.

A study was performed at Kuwait University by Adekile et al. (2005) on a cohort of 68 Kuwaiti sickle cell (SS) patients aged 7 to 44 years and 167 healthy age- and sex- matched controls to investigate HLA-DRB1 alleles. Out of the 68 patients, 20 suffered from avascular necrosis of the femoral head (AVNFH) and the diagnosis was confirmed through magnetic resonance imaging. Significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) was revealed through the contrast of HLA alleles among the cohort and the control groups. Meanwhile, no significant distinction was found in the allele frequencies among SS patients with or without AVNFH. Adekile et al. (2005) demonstrated that HLA-DRB1 had no significant role in the pathogenesis of AVNFH Kuwaiti patients.

Alsaeid et al. (2006) investigated the association of the HLA DRB1 alleles in Kuwaiti patients with rheumatoid arthritis (RA). DRB1 alleles were analyzed in 47 Kuwaiti patients and 70 ethnically matched controls using a DNA-based sequence specific primer (SSP) method. The frequency of DRB1*04 allele was found to be higher in patients compared to the controls (P < 0.012). The association with of HLA-DRB1*04 allele in these patients with RA was accounted for mainly by the seropositive group of patients (P < 0.05). Moreover, five patients were found to be homozygous for DRB1*4 compared to none in the controls. None of the other DRB1 alleles tested was found to be significantly higher in the patients. All patients homozygous for the DRB1*04 allele were found to be females. No statistically significant difference was found in the frequency of DRB1*04 allele in patients classified according to presence of erosive disease or extra-articular manifestations. Alsaeid et al. (2006) concluded that the results of this study indicate that in Kuwaiti patients, RA is associated with the presence of DRB1*04 allele, and the lack of association with severity or the phenotype of RA is not surprising since this is a hospital-based study where patients tend to have a more severe disease.

Allele frequencies of HLA Class II alleles, including HLA DRB1 alleles were studied in the Lebanese population by Cano et al (2012), Khansa et al (2012), Almawi et al (2004a), Almawi et al (2004b), and Samaha et al (2003).  

The contribution of HLA-DRB1 alleles to Type I Diabetes Mellitus susceptibility was studied in the Lebanese population by Al-Jenaidi et al (2005), Stayoussef et al (2009), and Ei Wafai et al (2011) Similar study on Type II Diabetes was conducted by Almawi et al (2006). 

Yamout et al (2016) found HLA-DRB1*15 to be the major factor for developing MS among Lebanese.

Aimagambetova et al. 2019 conducted a retrospective study, which compared HLA-DPB1, HLA-DQB1, and HLA-DRB1 alleles and DPB1-DQB1-DRB1 haplotypes of 93 Lebanese women with idiopathic recurrent pregnancy loss (RPL) to a control group of 113 Lebanese women with two or more successful pregnancies, and no miscarriages. Allele frequencies of DRB1*04:01:01 and DRB1*08:01:01 were significantly higher in RPL cases than in control women. However, DRB1*07:01:01, DPB1*04:01:01, and DRB1*14:01:01  allele were observed to have significantly lower frequencies in women with RPL than in control women. Haplotype analysis revealed positive association of RPL with DPB1*04:01:01-DQB1*03:02:01-DRB1*04:01:01, whereas DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 was observed in lower frequencies among RPL cases suggesting an RPL-protective nature.

[See: Bahrain > Stayoussef et al., 2009].

Al-Swailem et al (2006) examined the frequency of HLA-DRB1 alleles amongst Saudi patients with Rheumatoid Arthritis.  The study included 70 patients (13 males, 57 females) and 70 healthy volunteers.  HLA typing using PCR-SSOP showed an increased frequency of the DRB1 *04 allele compared to the controls.  High resolution typing of this allele indicated a positive association of the DRB1 *0405 allele with a significant relative risk, while the DRB1 *0403 allele showed a negative association.  The other alleles with increased frequency in the patient group were DRB1 *08 and DRB1 *10.  On the other hand, DRB1 *06 showed a negative association with RA.

[See: Bahrain > Stayoussef et al., 2009].

Al-Yafei et al. 2020 studied the distribution of HLA alleles in 77 unrelated Emiratis. The common HLA-DRB1 alleles identified among these subjects were DRB1*03:01:01 (16%) and DRB1*07:01:01 (15%). The study observed elevated level of heterozygosity at HLA-DRB1, HLA-A, and HLA-B loci.

Arnaiz-Villena et al. 2019 characterized HLA alleles in 52 blood donor volunteers from Abu Dhabi, UAE. HLA typing was carried out for HLA-A, HLA-B, HLA -C, HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles. Twenty-seven HLA-DRB1 alleles were identified in these subjects.

Creary et al. 2021 characterized HLA alleles and diversity across populations worldwide. One populaiton involved 52 Emirati individuals (104 chromosomes). HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1 alleles were typed in this population. 28 unique HLA-DRB1 alleles were identified in the Arab population.  

Tay et al. 2021 identified three HLA-DR4 haplotypes in seven children with type I diabetes from five Emirati families: HLA-DRB1∗04:01:01-DQB1∗03:02:01:01; HLA- DRB1∗04:02:01-DQB1∗03:02:01; and HLA-DRB1∗04:05:01-DQB1∗02:02:01:02. These haplotypes were previously associated with Type 1 Diabetes in Arabs. The study study additionally reported on HLA-DR4 and HLA-DR3 T1D risk haplotypes in the parents. Haplotypes HLA -A*26-B*08-DRB1*03 and HLA -C∗06-B∗50-DRB1∗03:01-DQ∗02 were also identified, previously associated with diabetes in North Indians. 

Alnaqbi et al. 2021 investigated the contribution of 20 HLA antigens to COVID19 severity in 115 Emirati patients. The study analyzed 20 HLA alleles involving HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1.HLA-B*51:01 and  HLA-A*26:01 was negatively associated with severity, whereas HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 was positively associated with severity.

Alvares et al. 2021 identified a novel HLA allele HLA-DRB1*01:01:36 in a potential Emirati bone marrow donor. HLA-DRB1*01:01:36 has three nucleotide changes from HLA-DRB1*01:01:01. The substitutions are at positions 5803 in exon 2 and 8777 and 8999 in exon 3. As these substitutions are silent mutations/intronic polymorphisms, they are predicted to not affect the protein structure.

Al-Yafei et al. 2022 studied HLA-DRB1 and HLA-DQB1 alleles to understand its association with type 1 diabetes (T1D) in 149 Emirati T1D patients. Four DRB1 alleles – DRB1*03:01, DRB1*04:02, DRB1*11:01, and DRB1*16:02 – showed significant allelic differences in patients and control subjects. Positive association with T1D was observed with diplotypes DRB1*03:01~DQB1*02:01, DRB1*04:02~DQB1*03:02, and DRB1*04:05~DQB1*03:02, whereas negative association was observed with diplotype DRB1*16:02~DQB1*05:02.