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Articles by R. Zhang
Total Records ( 6 ) for R. Zhang
  Q Feng , Z Fang , Z Yan , R Xing , L Xie and R. Zhang
 

We previously identified a matrix protein, MSI7, from pearl oyster Pinctada fucata. According to the structural analysis, the DGD site in the N-terminal of MSI7 is crucial for its role in the shell formation. In this study, we expressed a series of recombinant MSI7 proteins, including the wild-type and several mutants directed at the DGD site, using an Escherichia coli expression system to reveal the structure–function relationship of MSI7. Furthermore, in vitro crystallization, crystallization speed assay, and circular dichroism spectrometry were carried out. Results indicated that wild-type MSI7 could induce the nucleation of aragonite and inhibit the crystallization of calcite. However, none of the mutants could induce the nucleation of aragonite, but all of them could inhibit the crystallization of calcite to some extent. And all the proteins accelerated the crystallization process. Taken together, the results indicated that MSI7 could contribute to aragonite crystallization by inducing the nucleation of aragonite and inhibiting the crystallization of calcite, which agrees with our prediction about its role in the nacreous layer formation of the shell. The DGD site was critical for the induction of the nucleation of aragonite.

  C. Hu , W. Jia , R. Zhang , C. Wang , J. Lu , H. Wu , Q. Fang , X. Ma and K. Xiang
 

Abstract

Aims  Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population.

Methods  We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured.

Results  Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively).

Conclusion  Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

  J. Lu , C. Hu , W. Hu , R. Zhang , C. Wang , W. Qin , W. Yu and K. Xiang
  Aims  Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes.

Methods  Three single nucleotide polymorphisms (SNPs) (rs10494366, rs12143842 and rs12029454) were genotyped in 1240 Type 2 diabetic patients (631 men and 609 women) and 1196 normal controls (433 men and 763 women). Individuals with overt diseases other than diabetes were excluded. Heart-rate corrected QT interval (QTc) was determined by standard 12-lead ECG and Bazett formula. Sex-pooled analysis and sex-specific analysis for genotype-phenotype association were both conducted.

Results  In the diabetic group, the rs12143842 T allele was associated with a 3.87-ms (= 0.014, empirical = 0.039) increase in QTc duration for each additional allele copy, while rs10494366 and rs12029454 exhibited no significant association with QTc. We found no evidence of association for the three SNPs in subjects with normal glucose regulation. No significant SNP-gender and -diabetes affection interaction was observed.

Conclusions  The genetic variant rs12143842 in NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Future studies in different populations are needed to validate this finding and to evaluate the impact of NOS1AP variants on cardiovascular events and sudden cardiac death in diabetic patients.

  Q. Fang , S. Chen , Y. Wang , S. Jiang , R. Zhang , C. Hu , C. Wang , F. Liu , K. Xiang and W. Jia
  Aims  Hepatocyte nuclear factor-1α (HNF-1α) regulates the expression of genes encoding proteins involved in glucose metabolism and insulin secretion. Mutations in the HNF-1α gene cause maturity-onset diabetes of the young Type 3. However, the mechanism leading to this disease has not been completely ascertained. Previously, we found a novel mutation in the regulatory element of the human HNF-1α gene in two Chinese diabetes pedigrees. The nucleotide at position -128 T was substituted by G (nt-128 T[RIGHTWARDS ARROW]G). In this study, we analysed the functional defect of nt-128 T[RIGHTWARDS ARROW]G in HNF-1α transcription activity.

Methods  Luciferase reporter gene assays were carried out to examine the functional characteristics of this mutant. Electrophoretic mobility shift assays and chromatin immunoprecipitation were performed to confirm the binding of nuclear proteins to oligonucleotides.

Results  The variant construct (nt-128 T[RIGHTWARDS ARROW]G) had a 1.65-fold increase in promoter activity compared with that of the wild-type construct in HepG2 cells and a 1.33-fold increase in MIN6 cells, respectively. The variant resided at a FOXA/HNF-3 binding site identified by a series of competitive electrophoretic mobility shift assays and antibody supershift analyses. The assays showed a differential binding affinity in the wild-type and the nt-128 T[RIGHTWARDS ARROW]G mutant fragments by FOXA/HNF-3. Chromatin immunoprecipitation indicated that FOXA/HNF-3 bound to this region in vivo. One nucleotide substitution in the FOXA/HNF-3 site in the human HNF-1α regulatory element caused an increase of HNF-1α transcriptional activity.

Conclusions  Our data suggested that this substitution in the promoter region affects DNA-protein interaction and HNF-1α gene transcription. The mutant may contribute to the development of diabetes in these two nt-128 T[RIGHTWARDS ARROW]G pedigrees of Chinese.

  R. Zhang , F. Jiang , C. Hu , W. Yu , J. Wang , C. Wang , X. Ma , S. Tang , Y. Bao , K. Xiang and W. Jia
  Aims  Metabolic disorders are independent risk factors for the development of Type 2 diabetes. The aim of the study is to test the association of LPIN1 variants with Type 2 diabetes and clinical characteristics in large samples of the Chinese population.

Methods  In the first stage, 15 single nucleotide polymorphisms within the LPIN1 region were selected and genotyped in 3700 Chinese Han participants. In the second stage, the single nucleotide polymorphisms showing significant association or trends towards association were genotyped in an additional 3122 samples for replication. Meta-analyses and genotype-phenotype association studies were performed after combining the data from the two stages.

Results  In the first stage, we detected that rs16857876 was significantly associated with Type 2 diabetes with an odds ratio of 0.806 (95% CI 0.677-0.958, P = 0.015), while rs11695610 showed a trend with Type 2 diabetes (odds ratio 0.846, 95% CI 0.709-1.009, P = 0.062). In the second stage, a similar effect of rs11695610 on Type 2 diabetes was observed (odds ratio 0.849, 95% CI 0.700-1.030, P = 0.096). The meta-analyses combining the information from the two stages showed a significant effect of rs11695610 on Type 2 diabetes with an odds ratio of 0.847 (95% CI 0.744-0.965, P = 0.012). Finally, the phenotype-genotype association analyses showed that rs11695610 was associated with 2-h plasma glucose (P = 0.040) and triglyceride levels (P = 0.034).

Conclusions  Our data implied that common single nucleotide polymorphisms within the LPIN1 region were associated with Type 2 diabetes and metabolic traits in the Chinese population.

  W. Yu , F. Zhang , W. Hu , R. Zhang , C. Wang , J. Lu , F. Jiang , S. Tang , D. Peng , M. Chen , Y. Bao , K. Xiang , C. Hu and W. Jia
 

Aim

There is a close link between electrocardiographic ventricular repolarization QT parameters and Type 2 diabetes. The aim of the present study was to assess the effects of QT-related and diabetes-related variants in KCNQ1 on QT interval in a Chinese population.

Methods

We recruited 2415 patients with Type 2 diabetes and 1163 subjects with normal glucose regulation in the present study. QT interval was obtained and the heart rate-corrected QT interval (QTc) was calculated using Bazett's formula. Four single nucleotide polymorphisms in KCNQ1 were selected (rs12296050, rs12576239, rs2237892 and rs2237895) and genotyped.

Results

 In participants with normal glucose regulation, the minor allele T of rs12296050 was associated with a 3.46-ms QTc prolongation under an additive model (P = 0.0109, empirical P = 0.0498). In patients with Type 2 diabetes, we did not find any association for the single nucleotide polymorphisms.

Conclusions

Our findings indicate that KCNQ1 is associated with QT interval in a Chinese population with normal glucose regulation.

 
 
 
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