[Influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection].

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected 660 million people and resulted in 6.7 million deaths. At present, a variety of risk factors related to the severity of COVID-19 have been identified, but whether allergic rhinitis and asthma will affect SARS-CoV-2 infection remains controversial. In general, there is no sufficient evidence to support that allergic rhinitis or asthma is a risk factor for increasing the rate of SARS-CoV-2 infection or aggravating the disease. Some studies even show that atopy may be a protective factor to alleviate SARS-CoV-2 infection, which is related to the decreased expression of angiotensin-converting enzyme 2, the receptor required for SARS-CoV-2 to enter cells, in atopic individuals. This paper reviews the influence of the severity and treatment of allergic rhinitis and asthma on SARS-CoV-2 infection, in order to provide some references for establishing strategies for prevention, risk stratification and treatment of COVID-19.

[Research progress on pollen food allergy syndrome].

Pollen food allergy syndrome (PFAS) is an IgE-mediated allergic reaction that occurs when some pollinosis patients ingest certain plant-derived food that contains cross-reactive allergenic components. PFAS is prevalent in both children and adult pollinosis patients. In most cases, PFAS symptoms are confined to the oropharynx and occur within several minutes after oral contact with food. Therefore, PFAS has been also referred as oral allergy syndrome (OAS). A small proportion of PFAS patients would experience systemic symptoms or anaphylaxis. Currently, the diagnosis of PFAS is mainly based on clinical history and allergic tests [skin prick tests and(or) serum specific IgE tests]. Oral provocation tests are used to verify atypical patients. Component-resolved diagnosis is essential for further precise diagnosis and treatment. Management options for PFAS include lifestyle adjustment, symptomatic medication, and immunotherapy. The efficacy and appropriate population for immunotherapy need further investigation. This article aims to update the knowledge on epidemiology, pathogenesis and clinical management of PFAS, thereby enhancing clinicians' understanding as well as treatment progress of this disease entity.

[The similar characteristics of IgG4-related disease and allergic diseases].

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

[Clinical characteristics of children with IgE-mediated cow's milk protein allergy].

Objective: To analyze the clinical characteristics of children with IgE-mediated cow's milk protein allergy (CMPA) and provide a basis for disease management and prevention. Methods: A cross-sectional study was conducted to analyze 142 children aged 0-12 years who were diagnosed with IgE-mediated CMPA in Capital Institute of Pediatrics Affiliated Children's Hospital from 2020 to 2022. There were 79 males (55.6%) and 63 females (44.4%), with an average age of 14 (8, 27) months. 61 cases (43.0%) were in the <1-year-old group, 54 cases (38.0%) in the 1-3-year-old group, and 27 cases (19.0%) in the >3-year-old group. Data on demographic data, clinical manifestations, mean wheel diameter of skin prick test and serum specific IgE level were collected. The serum cow's milk protein sIgE and component sIgE were measured by ImmunoCAP fully automated system of fluorescence enzyme-linked immunosorbent assay, and statistically analyzed using chi-square test, nonparametric tests, correlation. Results: Cutaneous symptoms were the first and most frequent in 142 children (97.9%, 139/142 cases), followed by digestive (29.6%, 42/142 cases) and respiratory symptoms (27.5%, 39/142 cases).The proportion of children with respiratory symptoms after consuming cow's milk was significantly higher in the>3 years age group than those in the infant and toddler groups(66.7% vs 19.7%,χ2=18.396,P<0.01;66.7% vs 16.7%,χ2=20.250,P<0.01), and the symptoms involving ≥3 systems were also significantly higher than those in the other two groups(37.0% vs 13.1%,χ2=6.597,P<0.05;37.0% vs 7.4%,χ2=12.120,P<0.01). The average cow's milk SPT diameter and serum sIgE levels in the>3 years age group were significantly higher than those in the infant and toddler groups (Z=-4.682, P<0.01; Z=-3.498, P<0.01); (Z=-4.463, P<0.01; Z=-6.463, P<0.01). The most common cow's milk component protein were ß-lactoglobulin(65.1%,56/86 cases) and casein (57.0%, 49/86 cases). Multiple-sensitization rate of the patients were 54.9%. Egg white (43.7%, 62/142 cases) was the most common co-sensitization food allergen while mold (12.7%, 18/142 cases) and weed pollen (12.7%, 18/142 cases) were the main co-sensitization aeroallergens. The proportion of multiple-sensitization to aeroallergens in the children group was the highest (51.9%, 14/27 cases), followed by the toddler group (29.6%, 16/54 cases), and the infant group was the least (3.3%, 2/61 cases). There was a significant difference among these three groups (χ2=7.476, P<0.05). Conclusion: Skin and mucosal symptoms are the most common in CMPA patients. The proportion of respiratory symptoms and multisystem involvement increased with age as well as the wheal diameter in skin test and serum sIgE level elevated. CMPA patients older than 3 years had the highest proportion of aeroallergen sensitization and airway allergic diseases.

[Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy].

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.

[Updates in diagnosis, treatment, and prevention of anaphylaxis to neuromuscular blocking agents and their antagonists].

Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.

[Progress on the diagnosis and therapy about atopic diseases and primary immunodeficiency diseases].

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.

Major histocompatibility complex (MHC) associations with diseases in ethnic groups of the Arabian Peninsula.

Since the discovery of human leukocyte antigens (HLAs), the function of major histocompatibility complex (MHC) gene families in a wide range of diseases have been the subject of research for decades. In particular, the associations of autoimmune disorders to allelic variants and candidate genes encoding the MHC are well documented. However, despite decades of research, the knowledge of MHC associations with human disease susceptibility have been predominantly studied in European origin, with limited understanding in different populations and ethnic groups. This is particularly evident in countries and ethnic populations of the Arabian Peninsula. Human MHC haplotypes, and its association with diseases, of the variable ethnic groups of this region are poorly studied. This review compiled published manuscripts that have reported a list of autoimmune diseases (insulin-dependent diabetes mellitus, systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, psoriasis vulgaris, and multiple sclerosis) associated with MHC class I and class II in the populations of the Arabian Peninsula, specifically Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, the United Arab Emirates, and Yemen. Data available was compared with other three ethnic groups, namely Caucasians, Asians, and Africans. The limited data available in the public domain on the association between MHC gene and autoimmune diseases highlight the challenges in the Middle Eastern region.

The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Association between type 2 diabetes mellitus & TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) has a multifactorial etiology involving a complex interplay between genes and the environment. The prevalence of T2DM among the countries of the Gulf Corporation Council (GCC), including the United Arab Emirates (UAE), ranks among the top 15 in the world. A number of studies have shown an increase in T2DM risk for the "TT" genotype at the rs4506565 and rs12255372 Single Nucleotide Polymorphisms (SNP) of the TCF7L2 gene. However, the association between TCF7L2 and T2DM still needs to be investigated in the UAE population. Therefore, this study analyzed the potential associations with rs4506565 and rs12255372 in UAE subjects. METHODS: For this case-control study, T2DM patients (n = 890) and healthy subjects (n = 686) were genotyped using a Taqman Real-Time PCR assay. Statistical analysis was performed with the resulting data using the R (version 3.3.1) and STATA (version 13) software packages. RESULTS: The rs12255372 SNP was significantly associated with T2DM (OR = 1.16, 95% CI = 1.00-1.34; P = .042). However, no significant association was found for the rs4506565 SNP (P = .120). After gender stratification, a significant association was found for both SNPs in males (Prs4506565 = .009 and Prs12255372 = .021). Interestingly, we found the interaction between the SNP rs4506565 with gender alone (P = .032) and in conjunction with BMI and age (P = .036) confers associations with T2DM. CONCLUSIONS: These findings suggest that the genetic variants of the TCF7L2 gene are associated with an increased susceptibility to T2DM, especially in Emirati males. Our study also highlights the impact of biological and environmental risk factors including age, BMI, and gender on the genetic susceptibility to T2DM.

Alternative polyadenylation events differ dramatically between Tongcheng and Large White pigs in response to PRRSV infection.

Alternative polyadenylation (APA) is a widespread post-transcriptional regulation mechanism that increases the biological complexity of transcriptome and proteome. However, it is unclear whether APA regulation plays a role in genetic resistance to porcine reproductive and respiratory syndrome virus (PRRSV). Here, we reported genome-wide APA regulation of porcine alveolar macrophages in PRRSV-resistant Tongcheng (TC) pigs and PRRSV-susceptible Large White (LW) pigs upon PRRSV infection. Using 3' mRNA sequencing strategy, we detected 75 981 high-quality APA sites in porcine alveolar macrophages of TC and LW pigs. Furthermore, 1202 and 1089 differentially expressed APA sites, as well as 79 and 117 untranslated region-APA switching genes were identified in TC pigs and LW pigs upon PRRSV infection respectively. The APA events in TC pigs and LW pigs were involved in different biological pathways, while APA events in TC pigs are directly associated with the immune response to PRRSV infection. In addition, we identified genetic variations affecting polyadenylation signal between TC pigs and LW pigs. These findings would provide helpful information on APA regulation for further understanding of genetic resistance to PRRSV.

[Appropriate protocol of treatment modulation for seasonal allergic rhinitis caused by cypress pollens].

Objective: To investigate appropriate protocol of treatment modulation for seasonal allergic rhinitis (AR) patients, in order to promote the implementation of personalized medicine. Methods: Total of 124 AR patients allergic to cypress pollens were recruited from January to February 2020 in Department of Allergy in Peking Union Medical College Hospital, 43 males and 81 females with an average age of (41±9) years. The patients were divided into two groups with block randomization method. In the first group, treatment was modulated every two days according to the average daily rhinoconjunctivitis symptom score of the last two days (short-term symptom-score group); while in the second group, therapy regimen was adjusted every week based on the Allergic Rhinitis Control Test (ARCT) score of the last week (long-term ARCT group). The treatment level was up-regulated when the cypress pollen count increased and stayed at a high level (step-up pharmacotherapy stage); and treatment was down-regulated while the pollen count decreased (step-down pharmacotherapy stage). Daily symptom scores, medicine scores, and ARCT scores of the two groups were recorded and compared. Results: During the whole cypress pollen season, the daily rhinoconjunctivitis symptom score of short-term symptom-score group was significantly lower than that in long-term ARCT group(2.4±1.0 vs 2.7±1.0, P<0.01), and the difference between the two groups was more pronounced in the step-up pharmacotherapy stage than that in the step-down pharmacotherapy stage, while there was no statistical difference between the daily medicine scores of the two groups (P>0.05). During the pollen rising period, the ARCT score of short-term symptom-score group was significantly better than that of long-term ARCT group (21(19, 22) vs 20 (17, 21), P=0.049); while in the pollen peak period and decreasing period, the ARCT scores of the two groups showed no statistical difference (P>0.05). The proportion of incompliance with doctor's advice was higher in long-term ARCT group compared to that in short-term symptom-score group (30.1% vs 6.7%, P<0.001). Conclusion: The protocol of treatment modulation for seasonal AR patients allergic to pollens should be developed flexibly according to the variation trend of pollen allergen exposure, so as to implement the idea of personalized medicine.

[The effect on patient life quality of prophylactic treatment to seasonal allergic rhinitis and related transcriptomics research].

Objective: The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis. Methods: This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age (t=0.381, P=0.706) and gender (χ²=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results: There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group (P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49,t=4.016, P=0.006). Conclusion: The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

[The characteristics and change of aeroallergens in children from 2015 to 2020 in a hospital of pediatric in Beijing].

Objective: To analyze the characteristics of clinical distribution and change of aeroallergens in children with allergic diseases from 2015 to 2020. Methods: Children who visited Capital Institute of Pediatrics affiliated Children's Hospital, suspected of allergic diseases and received serum aeroallergens specific immunoglobulin E (sIgE) test were retrospectively enrolled (1 to 14 years old). sIgE was detected by Phadia1000 system with radioallergosorbent test fluorescent enzyme-linked immunoassay. The characteristics and change of the aeroallergens among the 6 years was analyzed. Enumeration data were expressed by percentage and categorical variables were compared by the independent samples t-test and Pearson χ2 test. Results: In total 4 608 tests (4 575 patients) of children were enrolled, the average age was (5.4±2.9) years old, with the median age of 5.0 years old. 3 176 were boys (68.9%), and 1 432 were girls (31.1%). 4 294 children were from the north of China (93.2%), 295 children were from the south of China (6.4%), and 19 children were from unknown regions (0.4%). In total the most common aeroallergen was mold mixture (1 956/4 457 tests, 43.9%) and Alternaria alternata (276/630 tests, 43.8%), followed by Artemisia (300/889 tests, 33.7%), Humulus scandens (12/38 tests, 31.6%) and grass mixture (909/2 874 tests, 31.6%). Among the 6 years, mold, grass pollen and tree pollen sensitization increased, and mold [38/130 (29.2%) vs 1 574/3 233 (48.7%)], grass pollen [11/77 (14.3%) vs 1 069/3 072 (34.8%)] increased significantly (χ2 was 18.953 and 49.559, respectively, P=0.000). Positive rate of tree pollen increased [1/10 (10.0%) vs 516/2 122 (24.3%)], but did not have statistical significance (χ²=1.111, P=0.292). Dust mite [36/146 (24.7%) vs 321/1 408 (22.8%)] and hair of pets [7/33 (21.2%) vs 321/1 408 (17.1%)] sensitization didn't change greatly (χ2 =0.258, P =0.611; χ2 =0.379, P =0.538). In 2015, the most common aeroallergens was mold (38/130, 29.2%), followed by dust mite (36/146, 24.7%), while in 2020, the most common aeroallergens was still mold (1 574/3 233, 48.7%), with grass pollen (1 069/3 072, 34.8%) and tree pollen (516/2 122, 24.3%) ranked after. Conclusion: Mold might be the most common aeroallergens in allergic children in Beijing area. With time went on, dust mite was gradually exceeded by grass pollen and tree pollen.

Stratified analyses of genome wide association study data reveal haplotypes for a candidate gene on chromosome 2 (KIAA1211L) is associated with opioid use in patients of Arabian descent.

BACKGROUND: Genome Wide Association Studies (GWAS) have been conducted to identify genes and pathways involved in development of opioid use disorder. This study extends the first GWAS of substance use disorder (SUD) patients from the United Arab Emirates (UAE) by stratifying the study group based on opioid use, which is the most common substance of use in this cohort. METHODS: The GWAS cohort consisted of 512 (262 case, 250 controls) male participants from the UAE. The samples were genotyped using the Illumina Omni5 Exome system. Data was stratified according to opioid use using PLINK. Haplotype analysis was conducted using Haploview 4.2. RESULTS: Two main associations were identified in this study. Firstly, two SNPs on chromosome 7 were associated with opioid use disorder, rs118129027 (p-value = 1.23 × 10 - 8) and rs74477937 (p-value = 1.48 × 10 - 8). This has been reported in Alblooshi et al. (Am J Med Genet B Neuropsychiatr Genet 180(1):68-79, 2019). Secondly, haplotypes on chromosome 2 which mapped to the KIAA1211L locus were identified in association with opioid use. Five SNPs in high linkage disequilibrium (LD) (rs2280142, rs6542837, rs12712037, rs10175560, rs11900524) were arranged into haplotypes. Two haplotypes GAGCG and AGTTA were associated with opioid use disorders (p-value 3.26 × 10- 8 and 7.16 × 10- 7, respectively). CONCLUSION: This is the first GWAS to identify candidate genes associated with opioid use disorder in participants from the UAE. The lack of other genetic data of Arabian descent opioid use patients has hindered replication of the findings. Nevertheless, the outcomes implicate new pathways in opioid use disorder that requires further research to assess the role of the identified genes in the development of opioid use disorder.

HLA class I allele lineages and haplotype frequencies in Arabs of the United Arab Emirates.

The high degree of polymorphism of the HLA system provides suitable genetic markers to study the diversity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low-resolution PCR-SSP genotyping of three HLA class I loci at HLA-A, -B and -C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE. A total of 54 HLA allele lineages were detected; the most frequent low-resolution allele lineages at each HLA locus were A*02 (0.268), B*51 (0.163) and C*07 (0.216). The inferred estimates for the two most frequent HLA-A and HLA-B haplotypes were HLA-A*02 ~ HLA-B*50 (0.070) and HLA-A*02 ~ HLA-B*51 (0.051), and the most frequent 3-locus haplotype was HLA-A*02 ~ HLA-B*50 ~ HLA-C*06 (0.068). The HLA allele lineage frequencies of the UAE Arabs were compared to those previously reported for 70 other world populations, and a strong genetic similarity was detected between the UAE Arabs and the Saudi Arabians from the west with evidence of a limited gene flow between the UAE Arabs and Pakistani across the Gulf from the east, and the UAE Arabs and Omani from the south of the Gulf Peninsula.

MHC class I polymorphic Alu insertion (POALIN) allele and haplotype frequencies in the Arabs of the United Arab Emirates and other world populations.

Polymorphic Alu insertions (POALINs) are found throughout the human genome and have been used in various studies to infer geographic origin of human populations. The main aim of this study was to determine the allele and haplotype frequencies of five POALINs, AluHF, AluHG, AluHJ, AluTF and AluMICB, within the major histocompatibility complex (MHC) class I region of 95 UAE Arabs, and correlate their frequencies to those of the HLA-A, HLA-C and HLA-B class I allele lineages. Evolutionary relationships between the POALINs of the Arabs and those previously studied in populations of African, Asian and European descent were compared. At each of the five Alu loci (AluHF, AluHG, AluHJ, AluTF and AluMICB), Alu insertion was designated as Alu(locus)*02 and absence was Alu(locus)*01. The AluHG insertion (AluHG*02) had the highest frequency (0.332), followed by AluHF*02 (0.300), AluHJ*02 (0.263), AluMICB*02 (0.111) and AluTF*02 (0.058). Of the 270 Alu-HLA haplotypes pairs in the UAE Arabs, 110 had no Alu insertion, and 54 had an Alu insertion at >50% per haplotype. An Alu insertion >75% per haplotype was found between AluMICB*02 and HLA-B*14, HLA-B*22, HLA-B*44, HLA-B*55, HLA-B*57 and HLA-B*73, and with HLA-C*01 and HLA-C*18; AluHJ*02 with HLA-A*01, HLA-A*19, HLA-A*24 and HLA-A*32; AluHG*02 with HLA-A*02 and HLA-B*18; and AluHF*02 with HLA-A*10. The genotyped allele and haplotype frequencies of the MHC POALINs in UAE Arabs were compared with the results of 30 previously published Asian, European, American and African populations. Phylogenetic and multidimensional scaling (MDS) analysis of the relative MHC POALINs allele and haplotype frequencies revealed that the UAE Arabs have a similar lineage to Caucasians and the most distant genetic relationship to the Waorani native American population of Ecuador. The structure of both the phylogenetic tree and the MDS analysis supports the Out of Africa theory of human evolution. The nature of the clusters suggests the Arabian Middle East represents a crossroads from which human populations migrated towards Asia in the east and Europe to the north-west.

A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE).

Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10-8 ), rs74477937 (p-value = 8.56 × 10-8 ) and rs78707086 (p-value = 8.55 × 10-8 ) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.

Multiple genetic variations confer risks for obesity and type 2 diabetes mellitus in arab descendants from UAE.

BACKGROUND: The United Arab Emirates (UAE) is one of the countries most threatened with obesity. Here we investigated associations between hundreds of single-nucleotide polymorphisms (SNPs) and the following obesity indicators: body mass index (BMI), waist circumference (WC), and height. We also investigated the associations between obesity-related genes with type 2 diabetes mellitus (T2DM). METHODS: We tested 87, 58, and 586 SNPs in a previous genome-wide significance level for associations with BMI (n = 880), WC (n = 455), and height (n = 897), respectively. For each trait, we used normally transformed Z scores and tested them with SNPs using linear regression models that incorporated age and gender as covariates. The weighted polygenic risk scores for significant SNPs for each trait were tested with the corresponding Z scores using linear regression models with the same covariates. We further tested 145 obesity loci with T2DM (464 cases, 415 controls) using a logistic regression model including age, gender, and BMI Z scores as covariates. RESULTS: The Mean BMI was 29.39 kg/m2, and mean WC was 103.66 cm. Hypertension and dyslipidemia were common obesity comorbidities (>60%). The best associations for BMI was in FTO, LOC284260 and USP37, and for WC in RFX7 and MYEOV. For height, the best association was in NSD1 followed by MFAP2 and seven other loci. The polygenic scores revealed stronger associations for each trait than individual SNPs; although they could only explain <1% of the traits' Z scores variations. For T2DM, the strongest associations were with the TCF7L2 and MC4R loci (P < 0.01, OR ~1.70), with novel associations detected with KCNK3 and RARB. CONCLUSIONS: In this first study of Arab descendants, we confirmed several known obesity (FTO, USP37, and RFX7), height (NSD1, MFAP2), and T2DM (TCF7L2, MC4R) associations; and report novel associations, like KCNK3 and RARB for T2DM.

A 1000 Arab genome project to study the Emirati population.

Discoveries from the human genome, HapMap, and 1000 genome projects have collectively contributed toward the creation of a catalog of human genetic variations that has improved our understanding of human diversity. Despite the collegial nature of many of these genome study consortiums, which has led to the cataloging of genetic variations of different ethnic groups from around the world, genome data on the Arab population remains overwhelmingly underrepresented. The National Arab Genome project in the United Arab Emirates (UAE) aims to address this deficiency by using Next Generation Sequencing (NGS) technology to provide data to improve our understanding of the Arab genome and catalog variants that are unique to the Arab population of the UAE. The project was conceived to shed light on the similarities and differences between the Arab genome and those of the other ethnic groups.