Frequency Of HLA-DQB1 Alleles Research Articles

HLA-DQB1 Allele Polymorphism Associated with Oral Submucous Fibrosis in Hunan, China.

44 OSF patients and 44 healthy volunteers were included in this study. To detect the expression frequency of HLA-DQB1 alleles in the two groups and analyze significant allelic subtypes and their relative risk, polymerase chain reaction (PCR) sequence-specific primers were used. Subsequently, based on the identification of differential genes, we compare the gene expression levels of OSF patients and healthy volunteers expressing differential genes by real-time quantitative PCR. The expression frequency of the HLA-DQB1 ∗05 : 02 allele in the OSF group (36.4%) was significantly higher than in the controls (13.6%), and exposure to the HLA-DQB1 ∗05 : 02 allele was strongly related to OSF (OR (95% CI) = 3.619 (1.257,10.421), Wald χ2 = 5.681, P=0.017). However, there were no significant differences in the allele expression frequencies of DQB1 ∗02 : 01, DQB1 ∗03 : 03, DQB1 ∗05 : 01, DQB1 ∗05 : 03, DQB1 ∗06 : 02, DQB1 ∗06 : 03, and DQB1 ∗06 : 04 in the OSF group compared with the controls (all P > 0.05). Furthermore, the relative expression level of the HLA-DQB1 ∗05 : 02 allele in the OSF group (3.98 ± 3.50) was significantly higher than in controls (0.70 ± 0.41). There are differences in the HLA-DQB1 allele polymorphisms between the healthy population and patients with oral submucosal fibrosis. Preliminarily, it is suggested that the HLA-DQB1 ∗05 : 02 allele, which has a strong correlation with OSF and great differential expression between patients with OSF and controls, might be a susceptibility gene for OSF in Hunan.

Association of HLA-DRB1 Alleles with Rheumatic Fever and Rheumatic Heart Disease: A Meta-analysis

ABSTRACT Background Rheumatic fever (RF) and its sequel rheumatic heart disease (RHD) is an autoimmune disease caused by an abnormal host immune response to group A streptococcus (GAS) infection. The HLA class II molecules are entailed in immune-mediated infectious, inflammatory, and autoimmune diseases including RHD. However, HLA class II genes are reported to be associated with RF/RHD across different populations with a very little consistency. Objective The aim of the study is to investigate the association between HLA class II genes and RF/RHD by meta-analysis. Methods A comprehensive literature search was conducted to identify all relevant case-control studies published before December 31, 2019. The data were extracted using standardized form and pooled odds ratio (OR) with 95% confidence interval (CI) are calculated to assess the strength of the association between HLA class II genes and RF/RHD. Results Thirteen studies for HLA-DRB1 alleles (1065 patients and 1691 controls) and eight studies for HLA-DQB1 alleles (644 patients and 1088 controls) were finally included. The meta-analysis showed a significantly higher frequency of HLA-DRB1*07 allele (OR = 1.68, P < .0001) in RF/RHD patients when compared to controls, while the frequency of HLA-DRB1*15 allele (OR = 0.60, P = .03) was significantly lower in RF/RHD patients than in controls. However, there were no significant differences in the frequency of HLA-DQB1 alleles between RF/RHD patients and controls. Conclusions The results of the meta-analysis suggest that the differential presentation of autoimmune peptides by HLA-DRB1*07 (susceptible) and HLA-DRB1*15 (protective) alleles with different affinities may play a crucial role in the pathogenesis of RF/RHD.

Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran

Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA-DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by χ2 test with Yate’s correction and Fisher’s exact test. The most frequent HLA-DRB1 alleles were *1103=4 (23%), *1502 (9.5%), *0701 (9%), *0301 (8.5%), *1101 (7.5%) and *1501 (6%) while HLA-DQB1*0301 (40%), *0201 (15%), *0502 (10.5%), *0303 (10%), *0602=3 (9.5%), and *0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1*0409, *0804, *1102, *1112, *1405, and HLA-DQB1*0503, *0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA-DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari.

Association between HLA-DQB1 alleles and HAM/TSP patients in Khorasan Province.

HTLVI-1 is the first human retrovirus with limited endemic regions in the world. The epidemiological studies have shown that the genetic background and immune response to the virus have a significant role in HTLV-I-associated diseases. Among the genes are involved in HTLV-I infection, the role of human leukocytes antigen (HLA) have been studied in different population. In the present study we examined the association between HLA-DQB1 alleles and HTLV-I infection in HAM/TSP patients, HTLV-I carriers and healthy controls in north east of Iran, Mashhad. The blood samples of 16 patients with HAM/TSP, 20 HTLV-1 carriers, and 30 healthy individuals were taken and DNA was extracted by salting out method. HLA-DQB1 typing was performed using PCR-SSP method and the frequency of HLA-DQB1 alleles were compared by Fischer Exact Test. There was a significant difference between HAM/TSP patients and healthy controls in the frequency of HLA-DQB1*07 (P=0.004, RR=7). Furthermore, we found that possession of HLA- DQB1*02 or HLA-DQB1*05 increased the risk of disease 1.5 times. The data presented here suggest that both HLA-DQB1*07 and HLA-DQB1*06 are associated with disease development.

Association of HLA-DQB1 with the development of osteoarthritis

Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of different joints in the body, which may lead to joint destruction and life disability. It is a complex disease of multifactorial etiology like genetic variation. Genetics is believed to be important in determining the susceptibility of OA. It was proven to be associated with histocompatibility locus antigen region. The aim of this study was to analyze of the frequencies of HLA-DQB1 alleles in OA Iraqi Arab Muslims. A cross–sectional case control comparative study included twenty six Iraqi Arab Muslims patients who had knee OA and admitted in the Orthopedic Department at Al-Kindy Teaching Hospital between September – 2012 to June – 2013, and compared to control ethnically matched group. HLA–DRQ1 genotyping was done by polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) method. There was an increased frequencies of HLA-DQB1*03:01:01 in patients with OA compared with healthy controls (P=0.0171, odds ratio=7.4118, 95% CI=1.4285-38.4564); also there were an increase in the HLA-DQB1* 02:01:01, HLA-DQB1* 0305 and *04 in patients with OA compared with the control group, but the differences were not statistically significant. Our results suggest a role of the HLA DQB1*03:01:01 system in the etiopathogenesis of OA.

Association between HLA-DQB1 gene and patients with acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) affects both children and adults. Survival in ALL has improved in recent decades due to recognition of its biological heterogeneity. Although children have higher remission and cure rates than adults, both populations have benefited from these improvements. Our aim in this study is to determine the association between HLA-DQB1 genes with childhood and adult ALL patients. To define this association, we compared HLA-DQB1 allele frequencies and allele carrier frequencies in a cohort of 135 adults and children with ALL with 150 controls, using polymerase chain reaction with sequence-specific primers. Allele carrier frequencies in childhood ALL show a deficiency in DQ2 (*0201) (P 0.049 and RR 0.75), but an increase in DQ5 (*0501-*0504) and DQ7 (*0301, *0304) compared to the control group (P 0.001 RR 1.89, P 0.003 RR 1.48, respectively). Allele carrier frequencies in adult ALL indicated an increase in DQ5 (*0501-*0504) (P0.045 RR 2.28). Allelic frequencies in childhood ALL revealed the same increase in DQ5 and DQ7, and a decrease in DQ2. In adult ALL it shows a decrease in DQ7. Therefore, our results in adult ALL were similar to childhood ALL addressing DQ5 allele carriers, which showed an increase in both age groups. We suggest that DQ5 could be more strongly considered as an ALL susceptibility allele, and that this allele may underlie a pathogenic phenotype with a major role in the immunologic process involved in both adults and children with ALL.

Association between HLA-DQA1, HLA-DQB1 and oral cancer

Cancer is one of the most common causes of morbidity and mortality. Genes whose products play a critical role in regulation of the immune response include the HLA antigen and cytokine families of genes. Oral cancer is common in men in developing countries, and its frequency is increased by using betel-quid, tobacco, and alcohol. The association between certain HLA Class I and Class II haplotypes and cancer has been documented in a variety of tumors. There was no previous data concerning the association of specific HLA Class II DQA1, DQB1 alleles, or haplotypes with oral cancer patients. In this study, we enrolled 134 Taiwanese patients with histologically confirmed oral cancer and 268 age- and gender-matched healthy Taiwanese adults as control group to investigate the association between HLA-DQA1, HLA-DQB1 allele frequencies and oral cancer patients by using polymerase chain reaction with sequence-specific primers. We found that both HLA-DQA1* and HLA-DQB1* allele frequencies in oral cancer patients revealed no significant difference from those of control groups. Haplotype frequencies of HLA*DQA1-0103-DQB1*0601 in oral cancer patients were significantly lower than those of the control group (odds ratio: 0.18, 95% confidence interval: 0.054–0.583, p c = 0.02). Our data suggest that HLA DQA1*0103-DQB1*0601 haplotype may be protective with regard to the development of oral cancer.

Association between human leukocyte antigen DQB1 gene polymorphisms and bronchial asthma among Mongolia and Han nationalities

Objective To investigate association between human leukocyte antigen DQB1 (HLADQB1 ) gene polymorphisms and bronchial asthma among Mongolian and Han nationalities. Methods Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect frequencies of HLA DQB1 genotypes and alleles in 50 cases of Han and 68 Mongolian asthmatic patients, and 50 Han and 54 Mongolian healthy controls, respectively. Difference in gene frequencies between the two nationalities was estimated by odds ratio (OR) and chi-square test. Results Frequency of the HLA-DQB1 0602 allele was significantly higher in Han patients with bronchial asthma than that in healthy Han nationality (OR = 6.163,P ＜0.01 ). Frequency of the HLA-DQB1 0603/0608 allele decreased in Mongolian asthmatic patients, as compared to that in healthy Mongolians ( OR = 0.199, P ＜ 0.05 ). Frequency of the HLA-DQB1 0301/4 allele was significantly higher in Mongolian asthmatic patients as compared to that in healthy Mongolians ( OR =2.074,P ＜0.05). Frequency of the HLA-DQB1 0301/4 allele was significantly higher in Mongolian than that in Han asthmatic patients ( OR = 2.482 ,P =0.05). Frequency of the HLA- DQB1 0602 allele was significantly higher in healthy Mongolians than that in healthy Han nationality ( OR = 3.341, P ＜ 0.05 ), in contrast, frequency of the HLA-DQB1 0402 allele was significantly lower in healthy Mongolians than that in healthy Han nationality ( OR = 0.209, P ＜ 0.05 ). Conclusions The HLA-DQB1 0603/0608 allele is possibly a protective gene and the HLA-DQB1 0301/4 allele a susceptible gene for bronchial asthma in Mongolians, and the HLA-DQB1 0602 allele is possibly a susceptible gene for bronchial asthma in Han nationlity. Key words: Asthma; HLA antigens; Mongolian nationality; Han nationality

Comparison of allele frequency for HLA-DR and HLA-DQ between patients with ECC and caries-free children

Early childhood caries (ECC) is one of the most common diseases of childhood. The etiology of ECC is multifactorial and both genetic and environmental factors play important roles in the pathogenesis of the disease. Genetic variations in the hosts may contribute to changes in the risk for dental caries. Genetic factors such as human leukocyte antigen (HLA) have recently been suggested as a predisposing factor. The aim of this study was to look for an association between HLA-DRB1 and HLA-DQB1 with ECC for developing new strategies for the diagnosis as well as the prevention of the disease. In this study, we extracted the genomic DNAs from whole blood samples of 44 patients with ECC and 35 caries-free children by the salting-out method. We amplified the genomic DNA by PCR-SSP and then HLA-typing was performed for all alleles. The results revealed a significant increase in the frequency of HLA-DRB1*04 in the patient group (P=0.019). The odds ratio for this allele was detected to be 10. The frequency of HLA-DQB1 alleles was not significantly different between the two groups. The above results suggest that HLA-DRB1*04 is associated with the susceptibility to ECC. Thus HLA-DRB1*04 detection as a molecular marker for early diagnosis of ECC may be recommended.

Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1∗15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1∗15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1,DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1∗15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1∗01,DQB1∗05 and HLA-DQA1∗01,DQB1∗06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.

Human leukocyte antigen-DQB1 alleles are not associated with schizophrenia in Kuwaiti Arabs.

Schizophrenia is among the most severe and debilitating of psychiatric disorders and has a complex mode of inheritance. A susceptibility locus has been identified on chromosome 6 and some association studies involving human leukocyte antigen (HLA) genes have reported diverse results. The objective of the present study was to determine if there is an association between HLA-DQB1 alleles and schizophrenia in Kuwaiti Arabs. The frequency of HLA-DQB1 alleles was determined in a cohort of 195 Kuwaiti Arabs consisting of 81 schizophrenia patients and 114 ethnically matched healthy controls, using a polymerase chain reaction-sequence specific primers method. A total of nine DQB1 alleles were identified in this Kuwaiti cohort. The most prevalent DQB1 alleles in Kuwaiti schizophrenia patients were *0601 (28%), *0201 (23%) and *0501 (16%), respectively. However, no significant difference in the allele frequency was detected between schizophrenia patients and the controls. The DQB1*0602 allele, which has been negatively associated in African-Americans in previous reports, was not detected in the present Kuwaiti schizophrenia patients or controls.

Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region.

The high incidence of insulin-dependent diabetes mellitus (IDDM) in Finland contrasts strikingly with the low rates in the neighbouring populations of countries in the Eastern Baltic region: Estonia, Latvia and Russia. To evaluate the possible contribution of genetic factors to these differences, the frequencies of HLA-DQB1 alleles and relevant DQB1-DQA1 or DQB1-DRB1 haplotypes associated with IDDM risk or protection were analysed among IDDM patients and control subjects from these four populations. An increased frequency of HLA-DQB1*0302, DQB1*02-DQA1*05 and DQB1*0302-DRB1*0401 was observed in subjects with IDDM in all studied populations, whereas the prevalence of DQB1*0301 and DQB1*0602 and/or *0603 was decreased among patients. The degree of IDDM risk associated with HLA alleles analysed here did not differ significantly between the populations. Comparisons of the distribution of IDDM-related HLA alleles and haplotypes in the background populations revealed its consonance with IDDM incidence. The combined frequency of high risk genotypes was significantly higher among Finns than in other populations studied. Our data support the hypothesis that variance in the dispersion of HLA alleles is the genetic basis of variation of IDDM incidence observed in the Eastern Baltic region.

Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukaemia.

Epidemiological studies suggest that childhood common acute lymphoblastic leukaemia (c-ALL) may be the rare outcome of early post-natal infection with a common infectious agent. One of the factors that may determine whether a child succumbs to c-ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of (human leucocyte antigen) HLA genes, an association between an HLA allele and c-ALL could provide support for an infectious aetiology. To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis. We find that a significant excess of children with c-ALL type for DQB1*05 [relative risk (RR): 2.54, uncorrected P=0.038], and a marginal excess with DQB1*0501 (RR: 2.18; P=0.095). Only 3 of the 62 children with c-ALL have the other susceptibility allele, DPB1*0201 as well as DQB1*0501, whereas 15 had one or the other allele. This suggests that HLA-associated susceptibility may be determined independently by at least two loci, and is not due to linkage disequilibrium. The combined relative risk of the two groups of children with DPB1*0201 and/or DQB1*0501 is 2.76 (P=0.0076). Analysis of amino acids encoded by exon 2 of DQB1 reveal additional complexity, with significant (P<0.05) or borderline-significant increases in Gly26, His30, Val57, Glu66-Val67 encoding motifs in c-ALL compared with controls. Since these amino acids are not restricted to DQB1*0501, our results suggest that, as with DPB1, the increased risk of c-ALL associated with DQB1 is determined by specific amino acid encoding motifs rather than by an individual allele. These results also suggest that HLA-associated susceptibility to c-ALL may not be restricted to the region bounded by DPB1 and DQB1.