3'UTR SNPs in the LPP gene associated with Immunoglobulin A nephropathy risk in the Chinese Han population.

The purpose of this study was to investigate the relationship between Lipoma preferred partner (LPP) gene polymorphisms and the risk of Immunoglobulin A nephropathy (IgAN) in the Chinese Han population. In this case-control study, we genotyped three single nucleotide polymorphisms (SNPs) of the LPP gene in 357 IgAN cases and 384 controls, using Agena Bioscience MassARRAY technology and assessed their association with IgAN using the χ2 test and genetic model analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess risk and were adjusted for age and gender by logistic regression. In the allele model, there were significant associations between LPP rs1064607 (OR = 1.24; 95% CI = 1.01-1.53; p = 0.041), rs3796283 (OR = 1.32; 95% CI = 1.08-1.63; p = 0.008), and rs2378456 (OR = 1.29; 95% CI = 1.05-1.59; p = 0.016), as well as an increased risk of IgAN. In the dominant model, the "G/C-C/C" genotypes of rs1064607 (p = 0.023), the "G/A-G/G" genotypes of rs3796283 (p = 0.0013) and the "G/C-C/C" genotypes of rs2378456 (p = 0.00052) were risk factors for IgAN. The results of the stratified analysis showed that rs3796283 and rs2378456 were connected with susceptibility to IgAN in different subgroups. Our data may provide new evidence to research the etiology of IgAN.

Genetic Variations rs859, rs4646, and rs372883 in the 3'-Untranslated Regions of Genes Are Associated with a Risk of IgA Nephropathy.

BACKGROUND: Previous studies indicate that genetic factors play an important role in the pathogenesis of IgA nephropathy (IgAN). To evaluate the association between single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'-UTR) of genes and IgAN risk, we performed a case-control study in a Chinese Han population. MATERIALS: Twelve SNPs were selected and genotyped in 384 IgAN patients and 357 healthy controls. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender. Multifactor dimensionality reduction (MDR) was used to analyze the interaction of SNP-SNP with IgAN risk. RESULTS: Our study demonstrated that IL-16 rs859 (OR = 0.75, p = 0.040) and CYP19A1 rs4646 (OR = 2.58, p = 0.017) polymorphism were related to the risk of IgAN. In stratified analyses by gender, CYP19A1 rs4646 (OR = 2.96, p = 0.015) and BACH1 rs372883 (OR = 1.81, p = 0.038) polymorphisms conferred susceptibility to IgAN in males. Besides, rs372883 reduced IgAN risk in females (OR = 0.44, p = 0.042). We also found rs859 polymorphism was correlated with grade I-II (OR = 0.42, p = 0.028) in subgroup analysis of Lee's classification. Additionally, we found rs4646 polymorphism was correlated with serum creatinine (p = 0.035). CONCLUSION: Our results suggested that the IL-16 rs859, CYP19A1 rs4646, and BACH1 rs372883 polymorphisms have potential roles in the genetic susceptibility to IgAN in Chinese Han population.

3'UTR variants of TNS3, PHLDB1, NTN4, and GNG2 genes are associated with IgA nephropathy risk in Chinese Han population.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and is characterized by mesangial cell proliferation and agglomeration of the mesangial matrix. METHODS: In this study, we aimed to explore the role of TNS3, PHLDB1, NTN4, and GNG2 3'untranslated region (3'UTR) polymorphisms with the risk of IgAN in a Chinese Han cohort. A logistic recession model was used to calculate the effects of candidate single nucleotide polymorphism (SNP) on IgAN risk after adjusting age and gender difference. In silico prediction was conducted to identify potential functions of SNPs. RESULTS: The analysis revealed a significant relationship between the homozygotic genotype for NTN4 rs1362970 A/A and higher risk of IgAN (p = 0.003). Statistically significant associations were found when the sample was stratified by gender and Lee's grade. As a result, NTN4 rs1362970 A/A and GNG2 rs3204008 G/G genotypes were associated with enhanced IgAN risk in males (p = 0.006, p = 0.023, respectively), and the association between the PHLDB1 rs7389 G/T genotype and higher IgAN risk was found in females (p = 0.008). In the Lee's grade III-V subgroup, the rs1369270 in NTN4 was significantly correlated with the risk of IgAN (p = 0.004). Bioinformatics prediction suggested that rs1362970 within NTN4 3'UTR was located in the potential target sequence of miR-483-5p. CONCLUSIONS: Our research confirmed that NTN4, GNG2, and PHLDB1 gene polymorphisms were implicated in IgAN susceptibility in Chinese Han population. Further research should be conducted to investigate and validate the mechanism by which the above-mentioned polymorphisms affect IgAN.

Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype Grs1800796A rs2069837G rs2069840 (P = 0.037) and G rs1800796A rs2069837C rs2069840 (P = 0.042) in IL-6were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN.

Association between MPHOSPH6 gene polymorphisms and IgA nephropathy risk in a Chinese Han population.

Multiple genetic and environmental factors together contribute to the risk of IgA nephropathy (IgAN). MPHOSPH6 play an important role in the recruitment of the exosome to the pre-rRNA. However, to date, little information is found about the association between MPHOSPH6 polymorphisms and the IgAN risk. In this case-control study, we genotyped five single nucleotide polymorphisms (SNPs) in MPHOSPH6 gene in 416 IgAN cases and 495 controls using Sequenom Mass-ARRAY technology and evaluated their association with IgAN using the χ2 and genetic model analysis. In the allelic model analysis, we determined rs1056654 was associated with a 0.774-fold decrease in the risk of IgAN (95%CI= 0.630-0.952; p = 0.015). In the genetic model analysis, we found that the "C/C" genotype of rs1056675 was associated with an increased risk of IgAN based on the codominant model (OR =1.48; 95% CI=1.03-2.13; p=0.033) and recessive model (OR =1.52; 95% CI=1.11-2.09; p=0.0095). The "G/A-A/A" genotype of rs1056654 was associated with a decreased risk of IgAN based on the dominant model (OR =0.75; 95% CI=0.58-0.98; p=0.032) and log-additvie model (OR =0.78; 95% CI=0.64-0.96; p=0.0188). Our data suggested that gene polymorphisms in the MPHOSPH6 may exert influences IgAN susceptibility in a Chinese Han population.

Association of genetic polymorphisms in IL-1R1 and IL-1R2 genes with IgA nephropathy in the Han Chinese population.

AIM: IgA nephropathy (IgAN) is the major cause of end-stage renal disease(ESRD) in Asia and its pathogenesis is influenced by both genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in IL1R1 and IL-1R2 may be associated with susceptibility to IgAN. In this study, we study the association between genetic variants of IL-1R1 and IL-1R2 and IgA nephropathy risk in the Chinese Han population. RESULT: In the allelic model analysis, the rs10490571 and rs3917225 were associated with a 1.40-fold, and 1.31-fold increased risk of IgA nephropathy, respectively. In the genetic model analysis, the rs10490571 in IL1R1 was associated with a 1.46-fold increased risk of IgAN in the dominant model and 1.36-fold increased risk in the Log-additive model, respectively. However, the rs3218977 in IL1R2 was associated with a 0.71-fold decrease risk of IgAN in the dominant model and a 0.71-fold decrease risk in the over-dominant model, respectively. We found four SNPs (rs11674595, rs4851521, rs719250, and rs3218896) constructed four haplotypes in the IL1R2 gene and none of the haplotype was significantly associated with risk of IgAN. MATERIALS AND METHODS: A case-control study was conducted including 426 nephropathy patients and 463 healthy controls. Chi-squared tests and genetic model were used to evaluate associations. >CONCLUSIONS: These findings suggested that IL-1R1 and IL-1R2 polymorphisms may contribute to the development of IgAN.

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients.

Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA. Compared with healthy controls, CAPD patients had increased TF, PAI-1 protein and mRNA expression by PBMCs at baseline and after stimulated by LPS (10 ng/mL) [p < 0.001]. The fasudil treatment resulted in a significant effect in decreasing TF and PAI-1 [p < 0.05] synthesis in PBMCs. TF and PAI-1 mRNA expression and activities in PBMCs were increased in CAPD patients. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients.

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells.

OBJECTIVE: To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells. METHODS: The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot. RESULTS: AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT. CONCLUSIONS: Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.