Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

Yoshikawa, Masahide; Asaba, Kensuke

doi:10.1038/s41598-020-70009-x

Cited by 5 publications

(6 citation statements)

References 41 publications

(79 reference statements)

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“…HELZ2 is involved in regulating the differentiation of adipocytes and could thus play a role in metabolism (Katano-Toki et al, 2013). PLA2R1, ITGB6, and SLIT3 putatively play a role in tumor suppression, however mutations at all of these loci are also known to influence variation in other phenotypes (Marlow et al, 2008; Hezel et al, 2012; Guo et al, 2013; Bernard and Vindrieux, 2014; Yu et al, 2014; Ng et al, 2018; Yoshikawa and Asaba, 2020). Most research on RHPN2 and PTK6 has focused on the role of their expression in cancer progression (e.g.…”

Section: Data Application To Estimate the Timing Of Selection On Neanderthal Allelesmentioning

confidence: 99%

The timing of human adaptation from Neanderthal introgression

Yair

Lee

Coop

2020

Preprint

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Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of Neanderthal adaptive introgression. From these, we identify cases in which Neanderthal introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation, contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples, and identifies cases of temporally varying selection that are sometimes shared across large geographic distances.

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Section: Data Application To Estimate the Timing Of Selection On Neanderthal Allelesmentioning

confidence: 99%

The timing of human adaptation from Neanderthal introgression

Yair

Lee

Coop

2020

Preprint

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“… 34 In addition, many SNPs have been reported to be a risk factor for idiopathic membranous nephropathy(rs4664308, rs3749117, rs35771982, and rs3823323). 35 36 37 In a study from Japan involving 941 consecutive inpatients presenting chest pain, it was found that PLA2R1 rs3749117 mutation was a risk factor for increased carotid intima-media thickness measured by a high-resolution B-mode ultrasonography (OR = 1.93, 95% CI:1.17–3.19, p = 0.01). 16 However, no relevant studies have explored the role and potential mechanism of action of PLA2R1 in the pathogenesis of MASLD.…”

Section: Discussionmentioning

confidence: 99%

Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD

Shao,

Ye,

Dong

et al. 2024

Hepatology Communications

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Background: Abnormal phospholipid metabolism is linked to metabolic dysfunction–associated steatotic liver disease (MASLD) development and progression. We aimed to clarify whether genetic variants of phospholipid metabolism modify these relationships. Methods: This case-control study consecutively recruited 600 patients who underwent MRI-based proton density fat fraction examination (240 participants with serum metabonomics analysis, 128 biopsy-proven cases) as 3 groups: healthy control, nonobese MASLD, and obese MASLD, (n = 200 cases each). Ten variants of phospholipid metabolism-related genes [phospholipase A2 Group VII rs1805018, rs76863441, rs1421378, and rs1051931; phospholipase A2 receptor 1 (PLA2R1) rs35771982, rs3828323, and rs3749117; paraoxonase-1 rs662 and rs854560; and ceramide synthase 4 (CERS4) rs17160348)] were genotyped using SNaPshot. Results: The T-allele of CERS4 rs17160348 was associated with a higher risk of both obese and nonobese MASLD (OR: 1.95, 95% CI: 1.20–3.15; OR: 1.76, 95% CI: 1.08–2.86, respectively). PLA2R1 rs35771982-allele is a risk factor for nonobese MASLD (OR: 1.66, 95% CI: 1.11–1.24), moderate-to-severe steatosis (OR: 3.24, 95% CI: 1.96–6.22), and steatohepatitis (OR: 2.61, 95% CI: 1.15–3.87), while the paraoxonase-1 rs854560 T-allele (OR: 0.50, 95% CI: 0.26–0.97) and PLA2R1 rs3749117 C-allele (OR: 1.70, 95% CI: 1.14–2.52) are closely related to obese MASLD. After adjusting for sphingomyelin level, the effect of the PLA2R1 rs35771982CC allele on MASLD was attenuated. Furthermore, similar effects on the association between the CERS4 rs17160348 C allele and MASLD were observed for phosphatidylcholine, phosphatidic acid, sphingomyelin, and phosphatidylinositol. Conclusions: The mutations in PLA2R1 rs35771982 and CERS4 rs17160348 presented detrimental impact on the risk of occurrence and disease severity in nonobese MASLD through altered phospholipid metabolism.

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“…PLA 2 R-related and THSD7A-related MN accounted for about 70% and 1–5% of IMN patients, respectively ( Zhang et al, 2021a ). A genome-wide association study indicated that single nucleotide polymorphisms in the PLA 2 R gene were closely related to IMN, which again revealed the involvement of this antigen by using an untargeted genetic approach ( Xu et al, 2020 ; Yoshikawa and Asaba, 2020 ). Other antigens including aldose reductase, superoxide dismutase-2, and α-enolase were also found in human, although their function remains to be established because they were not detected on normal podocyte surfaces ( Prunotto et al, 2010 ).…”

Section: Introductionmentioning

confidence: 97%

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy

et al. 2022

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Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which is the leading glomerular disease that recurs after kidney transplantation. Treatment for MN remained controversial and challenging, partly owing to absence of sensitive and specific biomarkers and effective therapy for prediction and diagnosis of disease activity. MN starts with the formation and deposition of circulating immune complexes on the outer area in the glomerular basement membrane, leading to complement activation. The identification of autoantibodies against the phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) antigens illuminated a distinct pathophysiological rationale for MN treatments. Nowadays, detection of serum anti-PLA2R antibodies and deposited glomerular PLA2R antigen can be routinely applied to MN. Anti-PLA2R antibodies exhibited much high specificity and sensitivity. Measurement of PLA2R in immune complex deposition allows for the diagnosis of PLA2R-associated MN in patients with renal biopsies. In the review, we critically summarized newer diagnosis biomarkers including PLA2R and THSD7A tests and novel promising therapies by using traditional Chinese medicines such as Astragalus membranaceus, Tripterygium wilfordii, and Astragaloside IV for the treatment of MN patients. We also described unresolved questions and future challenges to reveal the diagnosis and treatments of MN. These unprecedented breakthroughs were quickly translated to clinical diagnosis and management. Considerable advances of detection methods played a critical role in diagnosis and monitoring of treatment.

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Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

Cited by 5 publications

References 41 publications

The timing of human adaptation from Neanderthal introgression

The timing of human adaptation from Neanderthal introgression

Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy

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