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Relationship of genetic variants in IL33 gene and IL1RL1 gene with HBV-related liver cirrhosis in Han Chinese population: Three case-control studies.
Infection, Genetics and Evolution 2021 June 29
INTRODUCTION: Previous studies have indicated that IL33/ST2 pathway is strongly involved in HBV-related liver diseases. The aim of this study was to determine the relationship of genetic variants in IL33/ST2 pathway with susceptibility of liver cirrhosis.
MATERIALS AND METHODS: The study subjects included 2632 samples of Han Chinese population, including 840 negative controls (NeC), 691 chronic hepatitis B (CHB), 680 HBV-related liver cirrhosis (LC), and 421 HBV-related HCC patients. DNA was extracted from peripheral blood. Genotyping of IL33-rs4742170, rs1048274, rs10975519 and IL1RL1-rs1041973 was performed using MALDI-TOF-MS.
RESULTS: After adjustment for age, sex, smoking and drinking, significant associations were observed for IL33-rs4742170, rs1048274, rs10975519 polymorphisms with LC risk. However, there was no association between IL1RL1-rs1041973 and LC risk. Negative controls with IL33-rs4742170 CC genotype showed 1.800 times more likely to develop LC compared with TT genotype. Negative controls with rs10975519(TC+CC) genotype showed 1.318 times more likely to develop LC compared with TT genotype. CHB cases with rs4742170(CC+TC) genotype showed 1.302 times higher susceptibility to develop LC compared with TT genotype. The IL33-rs1048274G allele occurred more frequently in LC group than HCC group in codominant model (AG/AA: P = 0.001, OR = 1.656, 95%CI = 1.221-2.247; GG/AA: P = 0.018, OR = 1.539, 95%CI = 1.077-2.198). The IL33 haplotype CG conformed by rs10975519C and rs1048274G was more frequent in LC group than NeC group and CHB group. Moreover, the IL33 haplotype CCG conformed by rs4742170C, rs10975519C and rs1048274G was more frequent in LC group than HCC group.
CONCLUSION: Our findings demonstrate the association of genetic variants in IL33 with susceptibility to liver cirrhosis. IL33-rs4742170C, rs1048274G, rs10975519C may serve as biomarkers for the risk of LC.
MATERIALS AND METHODS: The study subjects included 2632 samples of Han Chinese population, including 840 negative controls (NeC), 691 chronic hepatitis B (CHB), 680 HBV-related liver cirrhosis (LC), and 421 HBV-related HCC patients. DNA was extracted from peripheral blood. Genotyping of IL33-rs4742170, rs1048274, rs10975519 and IL1RL1-rs1041973 was performed using MALDI-TOF-MS.
RESULTS: After adjustment for age, sex, smoking and drinking, significant associations were observed for IL33-rs4742170, rs1048274, rs10975519 polymorphisms with LC risk. However, there was no association between IL1RL1-rs1041973 and LC risk. Negative controls with IL33-rs4742170 CC genotype showed 1.800 times more likely to develop LC compared with TT genotype. Negative controls with rs10975519(TC+CC) genotype showed 1.318 times more likely to develop LC compared with TT genotype. CHB cases with rs4742170(CC+TC) genotype showed 1.302 times higher susceptibility to develop LC compared with TT genotype. The IL33-rs1048274G allele occurred more frequently in LC group than HCC group in codominant model (AG/AA: P = 0.001, OR = 1.656, 95%CI = 1.221-2.247; GG/AA: P = 0.018, OR = 1.539, 95%CI = 1.077-2.198). The IL33 haplotype CG conformed by rs10975519C and rs1048274G was more frequent in LC group than NeC group and CHB group. Moreover, the IL33 haplotype CCG conformed by rs4742170C, rs10975519C and rs1048274G was more frequent in LC group than HCC group.
CONCLUSION: Our findings demonstrate the association of genetic variants in IL33 with susceptibility to liver cirrhosis. IL33-rs4742170C, rs1048274G, rs10975519C may serve as biomarkers for the risk of LC.
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