[Study of the mechanism underlying the effect of SOCS3 rs4969170 A/G polymorphism on the occurrence of insulin resistance in chronic hepatitis C patients].
OBJECTIVE
To study the mechanism underlying the effect of the SOCS3 rs4969170 A/G alleles on the occurrence of insulin resistance (IR) in patients with chronic hepatitis C.


METHODS
The promoter region of the SOCS3 gene was amplified by PCR,and luciferase expression vectors were constructed and transfected into HepG2,Huh7 cell lines.The relative luciferase activity of each expression vector was assessed by the dual luciferase reporter gene assay system.Western blotting was used to detect SOCS3 protein expression in PBMCs from groups of patients with the rs4969170 AA and AG genotypes.The state of IR in eight patients was evaluated by determining their HOMA-IR.


RESULTS
The pGL3-A, PGL3-G and pGL3-control vectors showed significantly different luciferase expression in the HepG2 cells (0.121 00 ± 0.022 07,0.027 00+/-0.012 49 and 0.043 33 ± 0.005 51; F =48.068, P=0.001) and in the Huh7 cell lines (0.164 70 ± 0.007 10,0.027 33 ± 0.017 04 and 0.033 67 ± 0.014 98; F =115.137, P=0.001). The expression of SOCS3 protein was significantly higher in the rs4969170 AA genotype group than in the AG genotype group (1.22 ± 0.40 vs. 0.30 ± 0.19; t =4.149, P=0.006).The IR index of patients with the rs4969170 AA genotype and the AG genotype was 4.11 ± 2.62 and 1.47 ± 1.01 respectively.There were three patients with IR in the rs4969170 AA genotype group and one in the rs4969170 AG group. There was no statistically significant difference between the two genotype groups (t=1.881, P=0.109).


CONCLUSIONS
The SOCS3 rs4969170 A haplotype may enhance transcriptional activity of the gene promoter to regulate gene expression, thereby increasing intracellular SOCS3 protein level and ultimately interfering with insulin signaling and causing IR in patients with chronic hepatitis C.
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
Fang
F
Li
Yingying
Y
Zheng
Cuiping
C
Shao
Xiaohong
X
Fan
Lifen
L
Wang
Na
N
Huo
Haiying
H
Lu
Chihong
C
Wu
Xiaoyuan
X
Xu
D045744:Cell Line, Tumor; D017930:Genes, Reporter; D005838:Genotype; D006239:Haplotypes; D019698:Hepatitis C, Chronic; D006801:Humans; D007333:Insulin Resistance; D008156:Luciferases; D020641:Polymorphism, Single Nucleotide; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D008156:Luciferases