Dataset Information

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy.

ABSTRACT: The aim of the present study was to explore the correlation between single nucleotide polymorphisms (SNPs) rs3840858 and rs2304921 in a specific ?-2,6 sialyltransferase gene, ST6GALNAC2, and the susceptibility to immunoglobulin (IgA) nephropathy (IgAN). The distributions of genotypes of SNPs rs3840858 and rs2304921 in ST6GALNAC2 were detected by direct sequencing. The distributions of the genotype and allele frequencies of rs3840858 in patients with IgAN were significantly different from those in the control group (genotypes, P=0.001; alleles, P=0.001). The DI genotype ratio (17.8%) in the IgAN group was higher than that in the control group (5.6%) and the I allele frequency (8.9%) in the IgAN group was higher than that in the control group (2.8%). Univariate logistic regression analysis indicated that rs3840858 polymorphism is a risk factor of IgAN (P=0.001). The risk of developing IgAN in individuals who carried the DI genotype was 3-fold higher than that in individuals who carried the DD genotype [odds ratio (OR)=3.676, 95% confidence interval (CI)=1.284-10.519], and the risk of developing IgAN in individuals who carried the I allele was higher than that in individuals who carried the D allele (OR=3.415, 95% CI=1.223-9.531). The distributions of the genotype (AA, AG and GG) and allele (A and G) frequencies of rs2304921 did not have a statistically significant difference between patients with IgAN and those without (P>0.05). The SNP rs3840858 in the ST6GALNAC2 gene may be associated with the risk of developing IgAN in the population studied; however, polymorphism of rs2304921 appears to be irrelevant to the risk of developing IgAN in this population.

SUBMITTER: Lu C

PROVIDER: S-EPMC4473512 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy.

Lu Chen C Li Wen-Lan WL Ma Yi-Ran YR

Experimental and therapeutic medicine 20150403 6

The aim of the present study was to explore the correlation between single nucleotide polymorphisms (SNPs) rs3840858 and rs2304921 in a specific α-2,6 sialyltransferase gene, ST6GALNAC2, and the susceptibility to immunoglobulin (IgA) nephropathy (IgAN). The distributions of genotypes of SNPs rs3840858 and rs2304921 in ST6GALNAC2 were detected by direct sequencing. The distributions of the genotype and allele frequencies of rs3840858 in patients with IgAN were significantly different from those i ...[more]

PMID: 26136946

Similar Datasets

Project description:ObjectiveTo compare the genetic architecture of susceptibility variants of IgA nephropathy (IgAN) in Chinese and Europeans.MethodsWe selected the independent genome-wide significant variants of IgAN in European population as candidate variants. Their associations, risk alleles, risk allele frequencies, odds ratios and population attributable risk scores were derived and calculated, then compared with those in the current Chinese population, including 1 194 IgAN patients and 902 controls. Using the significant variants, genetic risk scores were calculated and compared between the East Asians and the Europeans. The correlation between the genetic risk scores and clinical manifestations was also evaluated.ResultsThere were 16 independent single nucleotide polymorphisms (SNPs) located in 11 loci showing significantly association with susceptibility to IgAN in the Europeans. 93.75% (15/16) of them also showed significant associations in the Chinese (P<0.05). The effects of all the associated SNPs were in the same direction, either risk or being protective for IgAN, between the Chinese and the Europeans. On the contrary, remarkable higher risk allelic odds ratio (P=1.94×10-2), higher risk allele frequency (P=3.09×10-2), and higher population attributable risk (P=3.03×10-4) were observed for most of the associated SNPs in the Chinese than in the Europeans. Furthermore, genetic risk scores were significantly larger in the Asian populations compared with the Europeans (P=1.78×10-163). While there was no significance among the subpopulations in both the East Asians and the Europeans. Compared with the healthy controls, the genetic risk score in the IgAN patients was significantly larger (P=3.60×10-27). Clinical analysis showed the genetic risk score was positively associated with serum levels of IgA and IgA1, phases of chronic kidney disease and Haas grades.ConclusionOur study provides further evidence in the shared genetic architecture between Chinese and Europeans, while differences with respect to the effect sizes and risk allele frequencies across ethnicities, contributing partially to the differences of disease prevalence.

Project description:IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N?=?4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N?=?10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P?=?5×10?³²-3×10?¹?), with heterogeneity detected only at the PSMB9/TAP1 locus (I²?=?0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P?=?2.5×10??). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r?=?0.30, P?=?3×10?¹²?). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

Dataset Information

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy.

Publications

Study of correlation between polymorphism of ST6GALNAC2 and susceptibility to IgA nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets