TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy

Thibaudin, Damien; Thibaudin, Lise; Berthoux, P; Mariat, Christophe; Filippis, J-P De; Laurent, B.; Alamartine, Éric; Berthoux, F

doi:10.1038/sj.ki.5002054

Cited by 36 publications

(26 citation statements)

References 33 publications

(38 reference statements)

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“…19 TNF contributes to the initiation and progression of renal injury. 20,21 Although the À308G-A polymorph- Genetic variants and chronic kidney disease T Yoshida et al ism of TNF 22,23 was earlier found to be associated with CKD, the À850C-T polymorphism of TNF has not been related to this condition. The variant T allele of the À850C-T polymorphism of TNF was associated with an increased risk of Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 99%

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

et al. 2009

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Although hypertension has been recognized as a risk factor for chronic kidney disease (CKD), the genetic factors for predisposition to CKD in individuals with hypertension remain largely unknown. The purpose of this study was to identify the genetic variants that confer susceptibility to CKD among individuals with hypertension. The study population comprised 3696 Japanese individuals with hypertension (2265 men, 1431 women), including 1257 individuals (789 men, 468 women) with CKD (estimated glomerular filtration rate (eGFR) o60 ml min À1 per 1.73 m 2 ) and 2439 controls (1476 men, 963 women; eGFRX60 ml min À1 per 1.73 m 2 ). The genotypes for 30 polymorphisms of 26 candidate genes were determined. An initial screening of allele frequencies by the v 2 -test revealed that eight polymorphisms were significantly (false discovery rate o0.05) associated with the prevalence of CKD in hypertensive individuals. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the T-C (Val591Ala) polymorphism of APOB (rs679899), the À681C-G polymorphism of PPARG (rs10865710), the T-C (Cys1367Arg) polymorphism of WRN (rs1346044), the À850C-T polymorphism of TNF (rs1799724), the À219G-T polymorphism of APOE (rs405509), the C-T polymorphism of PTGS1 (rs883484) and the 41A-G (Glu14Gly) polymorphism of ACAT2 (rs9658625) were significantly (Po0.05) associated with the prevalence of CKD. Our results suggest that APOB, WRN, ACAT2, APOE, PPARG, TNF and PTGS1 are susceptibility loci for CKD among Japanese individuals with hypertension. Determination of the genotypes for these polymorphisms may prove informative for the assessment of genetic risk for CKD among such individuals.

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Section: Discussionmentioning

confidence: 99%

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

et al. 2009

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“…To the best of our knowledge, this association is the first found between genetic variants and clinical outcome in IMN. Thibaudin et al (40) reported an association study of TNF-a gene polymorphisms with IMN. This group found a significant association of a SNP in the promoter region and a downstream microsatellite of the TNF-a gene with IMN susceptibility.…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy

Bullich

Ballarín

Oliver³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ a-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease.Design, settings, participants, & measurements A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed.Results This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. ConclusionThis study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.

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“…It has been hypothesized that cytokines generated in the airways in response to air pollution can spill over into the circulation, influencing autoimmune responses and distant events [89]. Air pollution increases the circulating levels of inflammation mediators, such as TNF-α, IL-6, and plasminogen activator inhibitor-1 [88, 90], and genetic polymorphisms in these cytokines are associated with the development of MN [91-95]. …”

Section: Environmental Studies Of Pmnmentioning

confidence: 99%

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

2018

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Background: Primary membranous nephropathy (pMN) is the most common cause of nephrotic syndrome in adults. The discovery of the 2 autoantigens, M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), has defined pMN as an autoimmune disease. A remarkable increase in the frequency of pMN in primary glomerular disease was witnessed in China. The genetic and environmental contributors to disease susceptibility have been investigated in these patients. Summary: We reviewed recent publications in genetic and environmental studies of pMN, focusing mainly on those undertaken in China. Following a genome-wide association study, the gene-gene interaction between the 2 most significant risk factors, PLA2R1 and DQA1, was validated in Chinese patients with MN. Fine mapping on human leukocyte antigen (HLA) locus found that DRB1*1501 and DRB1*0301 were risk alleles. Three amino acid residues on positions 13 and 71 of HLA-DRβ1 chain may confer the susceptibility to pMN by presenting T-cell epitopes on PLA2R. Another study found that DRB3*0202 was the most likely culprit allele for the signal at DRB1*0301. One environmental risk factor for pMN has been identified as the long-term exposure to high levels of PM_2.5 in Chinese patients with MN. Each 10 μg/m³ increase in PM_2.5 concentration was associated with 14% higher odds for pMN in the regions with PM_2.5 above 70 μg/m³. Key Message: A gene-environment interaction is suspected as an underlying mechanism for the increasing trend of pMN in China.

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TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy

Cited by 36 publications

References 33 publications

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension

HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

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