Association of Nephronophthisis 4 genetic variation with cardiorenal syndrome and cardiovascular events in Japanese general population: the Yamagata (Takahata) study

2021 ◽  
Author(s):  
Yoichiro Otaki ◽  
Tetsu Watanabe ◽  
Junya Sato ◽  
Yuta Kobayashi ◽  
Tomonori Aono ◽  
...  
2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Otaki ◽  
T W Watanabe ◽  
J G Goto ◽  
Y S Saito ◽  
T A Aono ◽  
...  

Abstract Background Nephronophthisis (NPHP) 4 gene encoding nephrocystin-4, which contributes to end-stage renal disease in children and young adults, is involved in the development of the heart and kidneys. Cardiorenal syndrome (CRS), which consists of bidirectional dysfunction of the heart and kidneys, is a risk factor for cardiovascular events. Single nucleotide polymorphisms (SNPs) within the NPHP4 gene are reportedly associated with kidney function, even in adults. However, the association of NPHP4 gene variability with CRS and cardiovascular events remains unknown. Purpose To examine whether NPHP4 gene variability is related to CRS and cardiovascular events in general population. Methods and results This prospective cohort study included 2,946 subjects who participated in a community-based health study with a 16-year follow-up period. We genotyped 11 SNPs within the NPHP4 gene whose minor allele frequency was greater than 0.1 in the Japanese population. The SNP rs12058375 was significantly associated with CRS and cardiovascular events. Multivariate logistic analysis demonstrated a significant association between the homozygous A-allele of rs12058375 with the presence of CRS. Haplotype analysis identified the haplotype with the A-allele of rs12058375 as an increased susceptibility factor for CRS. Kaplan-Meier analysis demonstrated that homozygous A-allele carriers of rs12058375 had the greatest risk of developing cardiovascular events among the NPHP4 variants. Multivariate Cox proportional hazard regression analysis revealed that the homozygous A-allele and heterozygous carriers of rs12058375 were associated with cardiovascular events after adjusting for confounding factors. The net reclassification index and integrated discrimination index were significantly improved by the addition of rs12058375 as a cardiovascular risk factor. Conclusion Genetic variations in the NPHP4 gene were associated with CRS and cardiovascular events in the general population, suggesting that it may facilitate the early identification of high-risk subjects with CRS and cardiovascular events. FUNDunding Acknowledgement Type of funding sources: None.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.


2011 ◽  
Vol 31 (12) ◽  
pp. 2990-2996 ◽  
Author(s):  
Stefan Stender ◽  
Ruth Frikke-Schmidt ◽  
Aristomenis Anestis ◽  
Dimitris Kardassis ◽  
Amar A. Sethi ◽  
...  

2012 ◽  
Vol 59 (13) ◽  
pp. E1393
Author(s):  
Jeffrey JW Verschuren ◽  
Judith A. Wessels ◽  
Stella Trompet ◽  
David J. Stott ◽  
Naveed Sattar ◽  
...  

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