Genome-wide association study of IgA nephropathy using 23 465 microsatellite markers in a Japanese population

Saka, Sanae; Hirawa, Nobuhito; Oka, Akira; Yatsu, Keisuke; Hirukawa, Takeshi; Yamamoto, Ryohei; Matsusaka, Taiji; Imai, Enyu; Narita, Ichiei; Endoh, Masayuki; Ichikawa, Iekuni; Umemura, Satoshi; Inoko, Hidetoshi

doi:10.1038/jhg.2015.88

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…Familial forms of IgAN have been reported worldwide, including in sibling pairs, families and extended pedigrees belonging to geographically isolated populations. A recent genome-wide association study (GWAS) identified multiple susceptibility loci coding for genes involved in critical mechanisms for the development of IgAN[42,43]. Identification of genes and pathways responsible for Gd-IgA1 and illness onset may ultimately lead to the development of novel therapeutic and prophylactic approaches.…”

Section: Discussionmentioning

confidence: 99%

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

Sun

Zhang

et al. 2016

PLoS ONE

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ObjectiveGalactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in cases of IgA nephropathy.MethodsPubMed, EMBASE, Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database were searched to identify eligible studies that evaluated a difference in aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta-analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd-IgA1) levels in different groups.ResultsA total of 22 studies (n = 1657) met inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20 studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells was higher in the IgAN group compared with healthy controls as well as in those with other renal diseases (SMD = 1.76, 95% CI = 1.18–2.34, P<0.00001; SMD = 1.05, 95% CI = 0.05–2.04, P = 0.04). The data synthesis suggested that IgAN patients had similar levels of serum Gd-IgA1, with no significant differences, compared with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN) patients (MD = 0.04, 95% CI = 0.00–0.08, P = 0.05; MD = -46.03, 95% CI = -217.70–125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there were no significant differences in Gd-IgA1 levels among patients with varying severities of IgAN (MD = 0.02, 95% CI = -0.02–0.05, P = 0.28).ConclusionsThe pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of cultured cells from peripheral blood or tonsils may be a useful biomarker for predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly associated with disease severity.

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Section: Discussionmentioning

confidence: 99%

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

Sun

Zhang

et al. 2016

PLoS ONE

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“…Interestingly, most of these loci are shared with other immune-related diseases. [12][13][14][15][16][17] One associated singlenucleotide polymorphism has been located within the ST6GAL1 gene. 16 ST6GAL1 encodes ST6 b-galactosamide a-2,6-sialyltranferase 1, a glycosyltransferase.…”

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confidence: 99%

IgA1 Glycosylation Is Heritable in Healthy Twins

Lomax-Browne

Visconti

Pusey

et al. 2016

JASN

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IgA nephropathy (IgAN) is the most common form of primary GN and an important cause of kidney failure. Characteristically, patients with IgAN have increased serum levels of undergalactosylated IgA1 (gd-IgA1). To assess the degree to which serum gd-IgA1 levels are genetically determined in healthy individuals, we determined serum IgA and gd-IgA1 levels by ELISA in a sample of 148 healthy female twins, including 27 monozygotic and 47 dizygotic pairs. Using the classic twin model, we found the heritability of serum gd-IgA1 and IgA levels to be 80% (95% confidence interval, 66% to 89%) and 46% (95% confidence interval, 15% to 69%), respectively. These data indicate that serum gd-IgA1 levels are highly heritable. Elucidating the genetic basis of this heritability will be important in understanding the pathogenesis of IgAN.

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“…This discrepancy was attributed mainly to the inclusion criteria (baseline proteinuria <0.5 g/d), the small sample size, or the interracial differences. An earlier gene study revealed that the differences between races influence the susceptibility [21, 22] to and progression of IgAN [23-26]. Barbour SJ, et al [27] analyzed the data of a cohort of 202 IgAN patients of self-reported Pacific-Asian origin and 467 of other origin obtained from the Toronto GN Registry (Toronto, Ontario, Canada) that were followed up for a median of 46.4 months.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features to Predict Progression of IgA Nephropathy with Mild Proteinuria

Ding

Liu

Duan

et al. 2018

Kidney Blood Press Res

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Background/Aims: In the past, little attention has been paid to patients with IgA nephropathy (IgAN) who had minimal proteinuria upon the onset. The aim of this study was to analyze the clinicopathological features and the prognostic factors in patients with IgA nephropathy. Methods: Data of patients that had their first renal biopsy in our hospital and were diagnosed with primary IgAN with proteinuria <1 g/d from January 1995 to December 2014 were retrospectively examined. Clinical records of the clinicopathological features, renal function, and proteinuria were collected and investigated. The factors affecting the renal function and proteinuria were analyzed by Cox regression. The predictive efficiencies of clinical and pathological models were evaluated by Harrell concordance index (C-index). Results: A total of 506 patients with IgA nephropathy were included in this study. (1) Baseline proteinuria greater than 0.5 g/d was positively associated with Oxford M, S, and T lesions. eGFR less than 90 mL/min/1.73 m² were positively associated with Oxford T. (2) In the follow-up with a median of 50 months, 82 patients (16.2%) achieved complete clinical remission (CCR), whereas 54 patients (10.6%) showed an increase in creatinine by more than 50% (not progressing to end-stage renal disease). The cumulative proportion of creatinine increased >50%, and the values obtained by life-table analysis in 10, 15, and 20 years were 15%, 21%, and 22%, respectively. Significant differences were found in baseline age, proteinuria, and Oxford T between the group of creatinine increase >50% and the CCR group. (4) Multivariate COX regression showed that baseline age and proteinuria > 0.5 g/d were independent risk factors of adverse outcome. C-index suggested that the clinical model was more effective than the pathological models in predicting endpoint events. (5) Effect of the mean value during the follow-up on adverse endpoint events: Multivariate COX regression found that the mean proteinuria during follow-up was an independent influencing factor for the increase of creatinine by more than 50%. Conclusion: (1) Proteinuria > 0.5g/d and eGFR < 90 mL/min/1.73 m² may predict more severe pathological changes; (2) With the increase in age and baseline proteinuria, the risks of adverse endpoint events would increase significantly; (3) Pathology could roughly predict the adverse endpoint events but is less efficient than the clinical indicators; (4) Data during follow-up suggested that the patients should regularly test their renal function and proactively control their proteinuria.

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Genome-wide association study of IgA nephropathy using 23 465 microsatellite markers in a Japanese population

Cited by 14 publications

References 32 publications

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review

IgA1 Glycosylation Is Heritable in Healthy Twins

Clinicopathological Features to Predict Progression of IgA Nephropathy with Mild Proteinuria

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