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Genetic Association of Human Leukocyte Antigens with Chronicity or Resolution of Hepatitis B Infection in Thai Population

الرابطة الوراثية لمستضدات كريات الدم البيضاء البشرية المزمنة أو حل عدوى التهاب الكبد الوبائي ب في السكان التايلانديين
Authors: Nawarat Posuwan; Sunchai Payungporn; Pisit Tangkijvanich; Shintaro Ogawa; Shuko Murakami; Sayuki Iijima; Kentaro Matsuura; +4 Authors

Genetic Association of Human Leukocyte Antigens with Chronicity or Resolution of Hepatitis B Infection in Thai Population

Abstract

Des études antérieures ont montré que les polymorphismes mononucléotidiques (SNP) dans les gènes HLA-DP, TCF19 et EHMT2 peuvent affecter l'hépatite B chronique (CHB). Pour prédire le degré de risque de chronicité du VHB, cette étude a déterminé des associations avec ces SNP. Les participants à cette étude ont été définis en 4 groupes : CHC (n = 230), CHB (n = 219), infection résolue par le VHB (n = 113) et sujets non infectés par le VHB (n = 123). Les SNP HLA-DP (rs3077, rs9277378 et rs3128917), TCF19 SNP (rs1419881) et EHMT2 SNP (rs652888) ont été génotypés. En raison d'une distribution similaire des fréquences de génotype dans HCC et CHB, nous avons combiné ces deux groupes (porteurs du VHB). La distribution des génotypes chez les porteurs du VHB par rapport à ceux qui ont résolu le VHB a montré que rs3077 et rs9277378 étaient significativement associés à des effets protecteurs contre le CHB dans le modèle dominant mineur (OR = 0,45, p<0,001 et OR = 0,47, p<0,001). Les autres SNP rs3128917, rs1419881 et rs652888 n'étaient pas associés aux porteurs du VHB. Les variations génétiques de rs3077 et rs9277378, mais pas rs3128917, rs1419881 et rs652888, étaient significativement associées aux porteurs du VHB par rapport au VHB résolu dans la population thaïlandaise.

Estudios previos mostraron que los polimorfismos de un solo nucleótido (SNP) en los genes HLA-DP, TCF19 y EHMT2 pueden afectar la hepatitis B crónica (CHB). Para predecir el grado de riesgo de cronicidad del VHB, este estudio determinó las asociaciones con estos SNP. Los participantes en este estudio se definieron en 4 grupos; CHC (n = 230), HBC (n = 219), infección por VHB resuelta (n = 113) y sujetos no infectados con VHB (n = 123). Se genotiparon los SNP de HLA-DP (rs3077, rs9277378 y rs3128917), SNP de TCF19 (rs1419881) y SNP de EHMT2 (rs652888). Debido a una distribución similar de frecuencias de genotipo en HCC y CHB, combinamos estos dos grupos (portadores de VHB). La distribución del genotipo en portadores del VHB en relación con aquellos que resolvieron el VHB mostró que rs3077 y rs9277378 se asociaron significativamente con efectos protectores contra CHB en el modelo dominante menor (OR = 0.45, p<0.001 y OR = 0.47, p<0.001). Los otros SNP rs3128917, rs1419881 y rs652888 no se asociaron con portadores del VHB. Las variaciones genéticas de rs3077 y rs9277378, pero no rs3128917, rs1419881 y rs652888, se asociaron significativamente con portadores del VHB en relación con el VHB resuelto en la población tailandesa.

Previous studies showed that single nucleotide polymorphisms (SNPs) in the HLA-DP, TCF19 and EHMT2 genes may affect the chronic hepatitis B (CHB). To predict the degree of risk for chronicity of HBV, this study determined associations with these SNPs.The participants for this study were defined into 4 groups; HCC (n = 230), CHB (n = 219), resolved HBV infection (n = 113) and HBV uninfected subjects (n = 123). The HLA-DP SNPs (rs3077, rs9277378 and rs3128917), TCF19 SNP (rs1419881) and EHMT2 SNP (rs652888) were genotyped.Due to similar distribution of genotype frequencies in HCC and CHB, we combined these two groups (HBV carriers). The genotype distribution in HBV carriers relative to those who resolved HBV showed that rs3077 and rs9277378 were significantly associated with protective effects against CHB in minor dominant model (OR = 0.45, p<0.001 and OR = 0.47, p<0.001). The other SNPs rs3128917, rs1419881 and rs652888 were not associated with HBV carriers.Genetic variations of rs3077 and rs9277378, but not rs3128917, rs1419881 and rs652888, were significantly associated with HBV carriers relative to resolved HBV in Thai population.

أظهرت الدراسات السابقة أن تعدد أشكال النوكليوتيدات المفردة (SNPs) في جينات HLA - DP و TCF19 و EHMT2 قد يؤثر على التهاب الكبد المزمن B (CHB). للتنبؤ بدرجة خطر الإصابة المزمنة بفيروس التهاب الكبد الوبائي بي، حددت هذه الدراسة الارتباطات مع هذه النيوكلوتايد. تم تعريف المشاركين في هذه الدراسة في 4 مجموعات ؛ فيروس التهاب الكبد الوبائي بي (ن = 230)، فيروس التهاب الكبد الوبائي بي (ن = 219)، تم حل عدوى فيروس التهاب الكبد الوبائي بي (ن = 113) و فيروس التهاب الكبد الوبائي بي (ن = 123). تم تنميط SNPs HLA - DP (rs3077 و rs9277378 و rs3128917) و TCF19 SNP (rs1419881) و EHMT2 SNP (rs652888). نظرًا للتوزيع المماثل لترددات النمط الجيني في HCC و CHB، قمنا بدمج هاتين المجموعتين (ناقلات HBV). أظهر توزيع النمط الجيني في ناقلات HBV بالنسبة لأولئك الذين حلوا HBV أن rs3077 و rs9277378 كانا مرتبطين بشكل كبير بتأثيرات وقائية ضد CHB في النموذج السائد الثانوي (OR = 0.45، p<0.001 و OR = 0.47، p<0.001). لم ترتبط SNPs الأخرى rs3128917 و rs1419881 و rs652888 بحاملات HBV. ارتبطت الاختلافات الجينية لـ rs3077 و rs9277378، ولكن ليس rs3128917 و rs1419881 و rs652888، بشكل كبير بحاملات HBV بالنسبة لـ HBV التي تم حلها في السكان التايلانديين.

Keywords

Male, Epidemiology, HLA-DP alpha-Chains, Gene, Linkage Disequilibrium, Epidemiology and Management of NAFLD, Gene Frequency, Histocompatibility Antigens, HLA-DP beta-Chains, Single-nucleotide polymorphism, Human leukocyte antigen, Hepatitis B Infection and Treatment, Q, Liver Neoplasms, R, Middle Aged, Thailand, Hepatitis B, Virus, Environmental health, Antigen, Medicine, Female, Research Article, Adult, Hepatitis B virus, Carcinoma, Hepatocellular, Genotype, Science, Immunology, Population, SNP, Polymorphism, Single Nucleotide, Hepatitis B, Chronic, Virology, Health Sciences, Genetics, Humans, Biology, Genetic Association Studies, Aged, Hepatology, FOS: Clinical medicine, Histone-Lysine N-Methyltransferase, HBV Infection, Hepatitis C Infection and Treatment, FOS: Biological sciences

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
26
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Average
Top 10%
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