Mouse anti-Human C4BPB monoclonal antibody, clone 2H0

A previous study of the authors using microarray analysis indicated that the expression of complement component 4 binding protein (C4BP)A is upregulated in essential hypertension (EH) patients, but the association between C4BPA variations and EH has not yet been clearly demonstrated. Since the 5' upstream region is known to serve important roles in the gene expression regulation, the present study aimed to identify and analyze the association of single nucleotide polymorphisms (SNPs) in the 5' upstream region between the C4BPA gene with EH in a case-control study among a northeastern Han Chinese population through direct sequencing as well as genotype detection. A total of 822 unrelated participants were included. The higher expression level of C4BPA in the peripheral blood of patients with EH was verified through reverse transcription-quantitative polymerase chain reaction and ELISA. A total of four SNPs, rs73079108, rs74148971, rs77660718 and rs11120211 were identified in the 5' upstream region of C4BPA. Association analysis demonstrated that the genotypic frequencies of rs73079108 were significantly different between EH and the control groups (P=0.011), and A allelic frequency was lower in EH (P<0.001). Logistic regression analysis indicated that the rs73079108 polymorphism was closely associated with EH (AA:GA:GG genetic model: P=0.007, odds ratio (OR)=0.604, 95% confidence interval (CI) [0.418-0.873]; AA+GA: GG genetic model: P=0.005, OR=0.806, 95% CI[0.382-0.841]), and the A allele may be a protective factor. Subgroup analysis by sex and BMI presented concordant conclusions in female and non-obese samples. Further analysis indicated that rs73079108 was associated with systolic blood pressure (P<0.001), diastolic blood pressure (P=0.001) and fast blood glucose (FBG) (P=0.021). In addition, rs73079108 GA and GG carriers reported a significant increase in the level of the protein encoded by C4BPA than those of AA carriers. The rs73079108 polymorphism in the 5' upstream region of C4BPA was associated with EH, and rs73079108-A may be an independent predictor.

Differential expression of the human genes coding for the alpha and beta polypeptides of the human C component C4b binding protein (C4BP) modulates the levels of C4BP molecules containing C4BP beta polypeptides, providing a mechanism to avoid the potential harmful effects of elevated concentrations of C4BP beta in plasma. To understand how the expression of the C4BPB gene is controlled, we have examined, in the major promoter of the human C4BPB gene, potential regulatory elements. A region from nucleotide -126 to +25 was able to drive high expression of a reporter gene in the human hepatoma cell line HepG2. A small subfragment of this region (from -126 to -90) is responsible for more than 90% of the promoter activity. Electrophoretic mobility shift assays revealed that transcription factors of the hepatocyte nuclear factor-3 (HNF-3) and nuclear factor-I (NF-I/CTF) families were able to bind to this region in a sequence-specific manner. We have characterized binding sites for these transcription factors and determined their relative contribution to the activity of the C4BPB promoter. The results suggest that cooperative interaction between HNF-3 and NF-I/CTF is required to obtain a full C4BPB promoter activity. Comparison of the structures of the C4BPA and C4BPB promoters reveals significant differences that could explain the differential transcription of the C4BP alpha and C4BP beta polypeptides during the acute phase response.