Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

Abstract

our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08-1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and Rcc risk in a population with low arsenic exposure. Renal cell carcinoma (RCC) represents the most deadly urological malignancy and accounts for 2 to 3% of all adult malignancies. RCC is most commonly diagnosed between the ages of 50 and 75 years old with a ratio of males to females of 1.5:1 1. The incidence of RCC in most countries has been increasing over the past decade 2. In Taiwan, the incidence trend and average annual percentage increase for kidney cancer from 2002 to 2012 was 5.1 and 2.9% for men and women, respectively 3. Although cigarette smoking, obesity, and hypertension have been identified as risk factors for RCC 4 , the etiology of RCC is still unclear.

Combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and environmental metals exposure on chronic kidney disease

“…Hence, the effect of NLRP3 rs4925650 GA/AA genotypes and NLRP3 rs10157379 CT/TT genotypes on susceptibility to CKD appears to be independent of age, sex, educational level, consumption of tea, alcohol, and coffee, analgesic usage, and disease histories of diabetes and hypertension. The present study found an association between the NLRP3 rs10157379 CT/TT genotypes and CKD in the Taiwanese population, which is in accordance with our previous research showed that the NLRP3 rs10157379 T allele has a borderline association with renal cell carcinoma 43 . These results imply that subjects with NLRP3 rs10157379 T allele may be associated with renal damage than those with C allele.…”

Associations of SMAD4 rs10502913 and NLRP3 rs1539019 Polymorphisms with Risk of Coal Workers’ Pneumoconiosis Susceptibility in Chinese Han Population

“… 31 It has been shown that the C allele of NLRP3 rs1539019 significantly increased the risk of renal cell carcinoma, and the genotype of CC was associated with increased renal cell carcinoma risk compared with AA genotype. 32 Previous studies suggested that the CC genotype of NLRP3 rs1539019 was not associated with altered major blunt trauma risk 33 and coronary heart disease risk. 34 In our study, we demonstrated that the CC genotypes at NLRP3 rs1539019 were not associated with CWP risk in the Chinese Han population.…”

In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach

“…Some NLRP3 gene variants (e.g. rs7512998 ) are significantly associated with hypertension [ 39 ]. Consequently, we may hypothesize that the outcome of COVID-19 is aggravated by the presence of T2DM, obesity and hypertension because patients with those conditions show an activated NLRP3 inflammasome which is probably further activated by the infection.…”