HLA-DRB1 Gene Polymorphisms Research Articles

Association of HLA-DRB1, HLA-DQB1 Alleles, and TNF-α Promoter Polymorphisms with Multiple Sclerosis in the Cuban Population

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the central nervous system. It is known that the Major Histocompatibility Complex class II region produces the most potent effect on MS genetic susceptibility. In addition, the genetic polymorphism within the TNF locus has been involved in the pathogenesis of various autoimmune diseases. This study has the purpose of evaluating HLA-DRB1, HLA-DQB1 alleles and TNF promotor alpha gene polymorphism (SNP TNF- α -238 G/A; - 243G/A; -308 G/A; -375 G/A, -856 C/T; -862 C/A) in a sample of Cuban MS patients. Disease-associated HLA susceptibility alleles were genotyped by the SSP-PCR method. The TNF- α genotypes were identified by sequencing. The association was found between HLA and MS, DRB1*15:01, DRB1* 14:01, DQA*01:02 and DQB1*06:02 being susceptibility alleles. TNF-α-308 G (OR=1,6, P<0,01) and TNF- α -238 G (OR=2,0, P<0,01) alleles had higher frequency among MS patients than control subjects. The odds ratio was increased among HLADRB1*1501 positive individuals. Our results have shown that the combination of TNF-α-238 G, -308 G with HLA-DRB1*15:01 and HLA-DQA1*01:02 increased susceptibility to MS (p<0.05 OR=4.2) in the Cuban population. Keywords: HLA, TNF-Alpha, polymorphism, SNP, Multiple Sclerosis, Cuban population

Association of HLA-DRB1, HLA-DQB1 Alleles, and TNF-α Promoter Polymorphisms with Multiple Sclerosis in the Cuban Population

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the central nervous system. It is known that the Major Histocompatibility Complex class II region produces the most potent effect on MS genetic susceptibility. In addition, the genetic polymorphism within the TNF locus has been involved in the pathogenesis of various autoimmune diseases. This study has the purpose of evaluating HLA-DRB1, HLADQB1 alleles and TNF promotor alpha gene polymorphism (SNP TNF- α -238 G/A; - 243G/A; -308 G/A; - 375 G/A, -856 C/T; -862 C/A) in a sample of Cuban MS patients. Disease-associated HLA susceptibility alleles were genotyped by the SSP-PCR method. The TNF- α genotypes were identified by sequencing. The association was found between HLA and MS, DRB1*15:01, DRB1*14:01, DQA*01:02 and DQB1*06:02 being susceptibility alleles. TNF-α-308 G (OR=1,6, P<0,01) and TNF- α -238 G (OR=2,0, P<0,01) alleles had higher frequency among MS patients than control subjects. The odds ratio was increased among HLADRB1*1501 positive individuals. Our results have shown that the combination of TNF-α-238 G, -308 G with HLA-DRB1*15:01 and HLA-DQA1*01:02 increased susceptibility to MS (p<0.05 OR=4.2) in the Cuban population. Keywords: HLA, TNF-Alpha, polymorphism, SNP, Multiple Sclerosis, Cuban population

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia

To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Association of mycoplasma pneumoniae and (rs9271366) HLA-DRB1gene polymorphism with the immune susceptibility to rheumatoid arthritis

Abstract Background: Rheumatoid arthritis (RA) is a chronic, inflammatory disease that affects the immune system. The primary cause of RA is unknown, but there is evidence that genetic and environmental factors also contribute to the development of the disease. Objectives: This study aimed to illustrate the relationship between the RA and Mycoplasma pneumoniae. Materials and Methods: The work was performed on 50 RA patients of various ages, ranging from 25 to 75 years of age, who were treated at the rheumatology clinic of the city of Medical Marjan between February 2022 to October 2022.Blood samples were used for DNA extraction. HLA-DRB1, IL-6 and mycoplasma were detected by enzyme-linked immunosorbent assay (ELISA). Results: The results showed that compared with RA patients not infected with Mycoplasma pneumoniae and healthy subjects, serum IL-6 concentration was significantly increased in RA patients infected with Mycoplasma pneumoniae. The results showed that serum concentrations of HLADRB1 were significantly elevated in RA patients infected with M. pneumoniae compared with RA patients not infected with M. pneumoniae and healthy subjects. Conclusions: In HLA-DRB1 the SNP rs9271366 was significantly associated with RA and G allele represent as dominant pathogenic allele in which the individual that carry GG and AG genotype have more susceptibility to mycoplasma infection than subjects that carry AA genotype (P = 0.036).

Study the association of Mycoplasma pneumoniae and (rs35445101) HLA-DRB1gene polymorphism with the immune susceptibility to rheumatoid arthritis

Abstract Background: Rheumatoid arthritis (RA) is an inflammatory immune disease that primarily affects the joints and has its root cause in immune system malfunction. It is unclear what causes RA, but research points to a combination of genetic predisposition, environmental exposures, and microbial infections. Objectives: This study aimed to illustrate the relationship between RA and Mycoplasma pneumoniae. Materials and Methods: The work was performed on 50 RA subjects of various ages, ranging from 25 to 75 years of age, who were treated at the rheumatology clinic in the city of Medical Marjan between February 2022 and October 2022. Blood samples were used for DNA extraction. VEGF-A.HLA-DRB1 and mycoplasma were detected by enzyme-linked immunosorbent assay. Results: The results show a significant increase in the serum concentration level of VEGF-A in RA patients infected with M. pneumoniae as compared to healthy individuals, but the results of RA patients with M. pneumoniae infections and RA patients without M. pneumoniae infections were nonsignificant (P &gt; 0.05). The results showed a significant increase in the serum concentration level of HLA-DRB1 in the RA patients infected with M. pneumoniae as compared to the RA patients noninfected with M. pneumoniae and healthy individuals. Conclusions: In HLA-DRB1, the SNP rs35445101 shows that A allele behavior as recessive pathogenic allele in which the individual that carries AA genotype has a susceptibility to the disease 9.75 fold compared to an individual that carries GG and AG genotype (odds ratio 9.75 confidence interval 95% 1.19–79.78).

HLA-DRB1 polymorphism and risk of pediatric-onset and adult-onset multiple sclerosis: a case–control study

The association of predisposition to multiple sclerosis (MS) with HLA-DRB1 gene polymorphisms is the strongest. It is not clear whether the DRB1 alleles associated with the risk of this disease diff er in adult and pediatric populations living in the same environmental conditions.Objective: comparative study of associations of HLA-DRB1 gene polymorphism with the risk of pediatric-onset MS and adult-onset MS in the Altai region.Material and methods. Caucasian with relapsing-remitting MS, born and living in the Altai region of Russia in the southeast of Western Siberia, participated in the case–control study: 200 patients with adult-onset MS, 86 patients with pediatric-onset MS. The control group included 200 volunteers. Genotyping was performed by TaqMan probes. Results. Alleles 03, 13, 15 of the HLA-DRB1 gene are genetic risk factors for both adult-onset MS and pediatric-onset MS in Caucasians in the Altai region. Alleles 01 and 07 of the HLA-DRB1 gene may have a protective eff ect against pediatric-onset MS, alleles 01, 07, 11 and 16 against adult-onset MS.Conclusion. It can be assumed that the diff erence in the age of MS onset is not associated with the diff erent infl uence of risk alleles of the HLA-DRB1 gene in populations under and over 18 years of age.

Prediction of response to anti-TNF treatment using laboratory biomarkers in patients with rheumatoid arthritis: a systematic review

ObjectivesIn this systematic review, we aim to identify laboratory biomarkers that predict response to tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).MethodsEMBASE, PubMed and Cochrane Library (CENTRAL)...

Investigation of HLA-DRB1 and IL28 gene polymorphism in patients with varying severity of COVID-19 infection

The work analyzed the polymorphisms of the HLA-DRB1 and IL28 genes in 100 patients who underwent COVID-19 with the development of infection with varying degrees of severity. To a mild degree of severity were patients without complications in the form of infectious pneumonate, to moderate and severe degrees - with the development of pneumonate with varying degrees of lung damage. In general, the distribution of alleles in patients with COVID-19 did not differ from the distribution of average values in Russia. However, the HLA-DRB1 *01 и *07 alleles were more common. Comparison of the frequency of HLA-DRB1 alleles in patients with COVID-19 with varying severity revealed more common alleles of *13 and *07 in the severety severe group. However, with OR of 3.2 and 1.8, their confidence intervals (CL) were in the range of 0.9-9.8 and 0.7-4.5 respectively. At severe severity, the presence of homozigotic variants of allele *07 is noted. (Fisher exact test, r.0.04). As for the IL28B gene, no statistically significant differences from the control group were found.

HLA-DRB1, IRF5, and CD28 gene polymorphisms in Egyptian patients with rheumatoid arthritis: susceptibility and disease activity.

This study was established to assess the effects of IRF5 rs10488631 and CD28 rs1980422 single-nucleotide polymorphisms (SNPs) and HLA-DRB1 shared epitope (SE) allele on the prognosis and disease activity of rheumatoid arthritis (RA) patients. A total of 150 RA patients and 150 healthy controls were genotyped for the selected SNPs by real-time PCR. HLA-DRB1 SE was determined using LAB Type SSO Class II DRB1 typing. Our results suggest that HLA-DRB1, CD28, and IRF5 significantly discriminated (p < 0.001) RA patients and healthy controls (OR of single HLA-DRB1 SE allele = 2.431, CI = 1.467-4.027, OR of two SE alleles = 11.152, CI = 2.479-50.159), (OR of CD28 risk allele C = 2.794, 95% CI = 1.973-3.956) and (OR of IRF5 risk allele C = 4.925, CI = 3.26-7.439). Rheumatoid factor (RF) seropositivity was associated with HLA-DRB1 SE (p < 0.001) and IRF5 risk allele (p < 0.001). ACPA was significantly associated only with IRF5 risk allele (p < 0.001). A better response to methotrexate therapy was found in HLA-DRB1 SE non-carriers, and CD28 TT patients. This study demonstrated associations of HLA-DRB1 SE, CD28, and IRF5 with the risk of RA. HLA-DRB1 SE and CD28 rs1980422 can be used as predictors of methotrexate therapy response.

Relationship between HLA-DRB1 gene polymorphism and breast cancer: A protocol for systematic review and meta-analysis.

Background:Breast cancer is one of the common malignant tumors in women, which seriously affects women's physical and mental health and even life-threatening. The occurrence and development of breast cancer are closely related to genetic factors. Many studies have shown that human leukocyte antigen DRB1 is associated with the development of breast cancer, but lack evidence. This study aims to systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer.Methods:The retrieval time of this study was from the establishment of the database to February 2021. The retrieval databases included CNKI, Wanfang, VIP and China Biomedical Database, PubMed, Embase, Web of Science, and the Cochrane Library. The retrieval objects were observational studies on the relationship between HLA-DRB1 gene polymorphism and breast cancer (including case--control studies, cross-sectional studies, and cohort studies). The language restrictions were English and Chinese. Two researchers independently extracted the data and assessed the quality of the included studies, and Stata 16.0 software was used for statistical analysis.Results:This study will systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer based on existing studies.Conclusion:This study will explore the early warning signal of breast cancer genetic susceptibility, and provide evidence-based medical evidence for clarifying the role of HLA-DRB1 gene polymorphism in breast cancer.OSF Registration number:DOI 10.17605/OSF.IO/847FQ

HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

Association of HLA-DRB1 Gene Polymorphism in Rheumatoid Arthritis Patients in Babylon Province, Iraq

Background: The heritability of rheumatoid arthritis (RA) is approximately 40% to 65% for seropositive RA and 20% for seronegative RA. The risk of developing RA has been associated with human leukocyte antigen HLA-DRB1 alleles: HLA-DRB1*04, HLA-DRB1*01, and HLA-DRB1*010 in deferent ethnocentrism. These HLA-DRB1 alleles contain a stretch of conserved five amino acid sequence, the shared epitope (SE), in the third hypervariable region of their DRB1 chain, which has been associated with the risk of developing Aim of the study: to study the possible association of HLA-DRB1 gene polymorphism of Arabic ethnocentrism PA patients in Babylon Province, Iraq. Patients and methods: The present case control study was conducted on sixty one patients (18 males and 43 females) of Arabic ethnocentrism RA patients admitted to Rheumatoid Unit in Merjan Teaching Medical City, Babylon Province, Iraq, as well as 127 apparently healthy control subjects (41 males, 86 females) as control group. Results: The risk of HLAD-RB1*01 allele was assessed through calculation of odds ratio (OR) which was estimated to be 1.95 (95 % confidence interval of 1.03 to 3.70). The risk of HLAD-RB1*04 allele was assessed through calculation of odds ratio (OR) which was estimated to be 4.46 (95 % confidence interval of 2.32 to 8.55). The risk of HLAD-RB1*010 allele was assessed through calculation of odds ratio (OR) which was estimated to be 3.12 (95 % confidence interval of 1.39 -7.00). Conclusion: The current study documented that RA is significantly associated with the locus HLA-DRB1* and allelic groups HLA-DRB1*01, HLA-DRB1*04 and HLA-DRB1*010 in Iraqi patients with RA

Vitamin D status in patients with multiple sclerosis: an association with insolation, disease course, and HLA-DRB1 gene polymorphism

Recent systematic reviews and a meta-analysis have shown that there is insufficient evidence on the relationship of multiple sclerosis (MS) to vitamin D supplementation Objective : to assess the relationship of vitamin D status in MS patients to insolation, disease course, and HLA-DRB1 gene polymorphism. Patients and methods. The one-stage study enrolled 90 patients with relapsing-remitting MS (a study group) and 87 volunteers without this disease (a control group). The enrolled were born and live in the Altai Territory of the Russian Federation. The serum level of 25(OH)D was measured by enzyme immunoassay. Results and discussion . 25(OH)D &lt;30 ng/ml was more common in patients with MS than that in the controls. There were no intergroup differences in the time spent in the sun for 6 months before inclusion in the study (p=0.020). The level of 25(OH)D was higher in the high insolation period from April to September than that in the low insolation period from October to March in both patients with MS (p&lt;0.005) and controls (p&lt;0.001). There was no association of 25(OH)D levels with urban and rural residence, gender, age at MS onset, severity of neurological disorders, their progression rate, and MS risk alleles within the HLA-DRB1 gene (03, 13, 15). Conclusion . Vitamin D deficiency is more common in patients with MS than in those without this disease. This is unlikely to be due to the differences in the radiation received from the sun. The final conclusion on the relationship of vitamin D to MS can be made after obtaining the results of a prospective follow-up.

The associations of HLA-DRB1 gene polymorphisms with late-onset myasthenia gravis: a meta-analysis.

Late-onset myasthenia gravis (LOMG) is one of the major subgroups of the MG. Intensive evidence suggested that polymorphisms in HLA-DRB1 gene were associated with LOMG risk, but the results remained inconsistent. Therefore, a meta-analysis is conducted to make a more precise evaluation between HLA-DRB1 alleles and LOMG. The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang and Technology of Chongqing (VIP) Database were searched for eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were applied to assess the association between HLA-DRB1 alleles and LOMG. A total of 11 studies involving 5513 people were included in our meta-analysis. The results showed that DRB1 07 and 0403 alleles were risk factors for LOMG (1.83 [1.12, 2.98], P = 0.02; 7.05 [2.62, 18.92], P = 0.0001, respectively), while DRB1 0301 and 1301 alleles were identified as protective factors for LOMG (0.44 [0.31, 0.62], P < 0.00001; 0.38 [0.23, 0.62], P = 0.0001, respectively). As for the HLA-DRB1 04 and 14 alleles, our subgroup analysis showed that there were significant associations between these alleles and LOMG in Caucasians (2.21 [1.14, 4.27], P = 0.02; 2.82 [1.29, 6.14], P = 0.009, respectively). These results confirmed the association of DRB1 alleles (0301, 04, 0403, 07, 1301, and 14) and LOMG, which might provide potential promising biomarkers for prediction of LOMG risk.

Concepts of Prakriti (Human Constitution) and its Association with Hematological Parameters, Body Mass Index (BMI), Blood Groups and Genotypes

Background: Ayurveda is an ancient system of personalized medicine, documented and practiced in India since 1500 B.C. According to this system an individual’s basic constitution to a large extent determines predisposition and prognosis to diseases as well as the therapy and life-style regime. Ayurveda describes seven broad Prakriti (Physical constitution) Prakriti is defined as the sum of physical, physiological, psychological traits of an individual which represents genotypes. Objective: In this article we have attempted to narrate concepts of Prakriti and its relation with hematological parameter, body mass index, blood groups and genotypes. Material and Method: Present article is based on critical review of Ayurvedic textual information, published research works, modern literature and research works conducted at various institutes. The possible correlation has been made between collected information and has been presented in systematic way. Result: In Pitta Prakriti individual’s hematological parameters like Hemoglobin (Hb%), Packed cell volume (PCV), and Red blood corpuscles (RBC) count are significantly on the higher side of normal range in comparison to Vata and Kapha Prakriti . Higher level of cluster of differentiation (CD) 14 markers in Pitta Prakriti , CD25 and CD56 in Kapha Prakriti individuals. Vata Prakriti individuals have “A” blood group, maximum Pitta Prakriti individuals have “O” blood group while maximum Kapha Prakriti individuals have “B” blood group and genotype correlation shows that HLA DRB1 ((human leukocyte antigen, dimer beta chain) gene polymorphism, CYP2C19 (Cytochrome P450 2C19) gene polymorphism and PGM1 (Phosphoglucomutase 1) polymorphism have scientific variations with the human Prakriti concept. Conclusion: Prakriti of individual has strong relation with Hematological parameters (CBC, lipid profile, Liver function test (LFT)), Body mass index (BMI), anthropometry, blood groups and genotypes.

Association of human leukocyte antigen-DRB1 with the response in patients with vitiligo

Background Vitiligo is a pigmentary disorder associated with the selective destruction of the skin melanocytes. Among the many human leukocyte antigen (HLA) alleles claimed to be incriminated in establishing vitiligo, HLA-DRB1 is included in many dermatological diseases and has been widely investigated in different studies worldwide. Aim To examine the susceptibility between HLA-DRB1 gene polymorphism and the therapeutic response of vitiligo. Patients and methods We performed a cohort study at Dermatology and Venereology Department, Zagazig Institution Hospitals from January 2018 to January 2019 on 80 patients with vitiligo who were subjected to treatment. Response to therapy was observed, and we followed up patients for 6 months. HLA-DRB1 genotyping using real-time PCR was performed once. Results The results showed that there was a significant statistical association regarding the therapeutic response in our study. Conclusion Our findings advise that DRB1 *0701 and *0413 are associated with good therapeutic response, whereas DRB1 *8 and *12 alleles are associated with worse therapeutic response among Egyptians.

Association of HLA-DR3 and HLA-DR15 Polymorphisms with Risk of Systemic Lupus Erythematosus.

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis.Methods:This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0.Results:A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316–1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334–2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320–1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248–2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370–1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078–1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738–2.490, P = 0.881, respectively).Conclusions:HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

Associations of human leukocyte antigen and interleukin-18 gene polymorphisms with viral load in patients with hepatitis B infection.

This study aimed to assess the associations of human leukocyte antigen (HLA)-DR and interleukin (IL)-18 gene polymorphisms with hepatitis B virus (HBV).Clinical data were retrospectively reviewed between December 2006 and December 2015 at Xiangyang Central Hospital. HBV patients were assigned to the high and low viral load groups, respectively, according to HBV copies. HLA-DRB1∗03 polymorphisms and IL-18 polymorphisms were detected by sequence-specific primer-polymerase chain reaction (PCR-SSP) and PCR-ligase detection reaction (PCR-LDR), respectively. T cell subgroups were identified by flow cytometry, and IL-18, IL-12, interferon-γ (IFN-γ), IL-4, and IL-10 expression levels were assessed by ELISA. A total of 630 subjects were included in the analysis.Compared with healthy controls, the chronic HBV group showed significantly lower IL-18 (P < .001), IL-12 (P < .001), and IFN-γ (P < .001) expression levels, and markedly increased IL-4 (P < .001) and IL-10 (P < .001) amounts. Th2 cytokine expression was high in HLA-DRB1∗03 positive (+) HBV patients, with low Th1 cytokine levels. The ratios of CD4+/CD8+ and Th1/Th2 cells decreased with increasing HBV DNA levels. The chronic HBV group showed a relatively high frequency of -137G in the IL-18 gene, while IL-18 expression was low in homozygous GG genotype individuals.Polymorphisms in the HLA-DRB1∗03 and IL-18 genes are associated with viral load in HBV. HLA-DRB1 and IL-18 gene polymorphisms are involved in the regulation of the Th1/Th2 balance and expression of relevant cytokines that influence immune responses in HBV.

Peculiarities of roentgenological picture of pulmonary tuberculosis upon HLA-DRB1 gene polymorphism depending on pro-and-antiinflammatory cytokines concentration

Aim. To study the peculiar features of roentgenological picture of pulmonary tuberculosis in patients with polymorphous HLA-DRB1 allels in the genotype in associations with pro-and-antiinflammatory cytokines concentration.&#x0D; Materials and methods. The complex clinicoimmunogenetic examination of 64 patients with pulmonary tuberculosis was carried out. The patients’ age ranged 18 to 52 years. The gene HLA-DRB1 polymorphism was determined using the method of polymerase chain reaction with DNA, previously extracted from blood samples. Cytokine concentration was determined in the peripheral blood before specific treatment, using the assay kits of “Vector-BEST Company” (Russia).&#x0D; Results. The prevailing clinical form of pulmonary tuberculosis among patients was infiltrative one – 40 (62.5). Bacterioexcretion was stated in 89.5 % of cases. Roentgenological picture of pulmonary tuberculosis in patients with HLA-DRB1 *04, *13, *14, *16 alleles was characterized as disseminated injury of lung tissue with destructive changes, the concentration of IL-1b, TNF-α exceeded the standard values by more than 3 times (r = 0.88; р = 0.040), IL-2, IL-10, g-INF was lower than standard values by more than 4–5 times (r = 0.75; р = 0.003).&#x0D; Conclusions. When studying HLA-DRB1 gene polymorphism and pro-and-antiinflammatory cytokines concentrations in patients with pulmonary tuberculosis, it was established that patients with HLA-DRB1 *01, *07, *08, *10, *15 alleles more often, compared to the others, had disseminated injury of lung tissue, in most cases with its destruction as well as dysbalanced cytokine balance in the direction of deep immunosuppression.

Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of "Treat to target" (REMARKA study).

To clarify the association between HLA-DRB1 and TNFα (-308G&gt;A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (&lt;6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to &quot;Treat to target&quot; strategy. The study included 85 patients with early RA and duration of symptoms &lt;6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G&gt;A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р&lt;0,005, and р&lt;0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р&lt;0,028, р&lt;0,019, р&lt;0,035 respectively). Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G&gt;A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to &quot;Treat to target&quot; stratagy.