A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

Palikhe, Sailesh; Udval, Uuganbayar; Trinh, Hoang Kim Tu; Ban, Ga‐Young; Yang, Eun‐Mi; Park, Hae‐Sim; Kim, Seung Hyun

doi:10.1155/2017/3549375

Cited by 8 publications

(4 citation statements)

References 38 publications

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“… 65 , 66 The functional impact of these variations, especially nonsynonymous polymorphisms, have been investigated in previous studies. 67 – 71 In genetic association studies of disease status and symptoms, SNPs or copy number variations within or around the ABCC4 gene have been shown to be associated with airway inflammation in asthmatic individuals, 68 unfavorable clinical outcomes in children with acute lymphoblastic leukemia, 69 patients with esophageal squamous cell carcinoma, 72 patients with chemotherapy-induced peripheral neuropathy, 73 and measures of pain symptoms in patients with lung cancer and acute post-radiotherapy pain. 74 , 75 However, none of these studies included the rs4773840 SNP or other SNPs that were in relatively strong LD with this SNP in our samples ( r 2 ≥ 0.8; Supplementary Figure S3).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

et al. 2021

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Background Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. Results Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain ( p ≥ 1.858 × 10−7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10−7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. Conclusions These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

et al. 2021

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“…Variant allele carriers of rs868853(C), which is located in the ABCC4 promoter, exhibited higher 2-AT+2-ATL levels than homozygous wild-type carriers (TT), and rs868853 was found to be an independent influence on plasma concentrations of 2-AT+2-ATL after adjusting for non-genetic factors by multiple linear regression. Palikhe et al showed asthma patients with the rs868853G allele had higher concentrations of asthma severity markers in blood and urine, and that the rs868853G SNP increased ABCC4 promoter transcriptional activity, suggesting that rs868853C may be associated with the transport of metabolites from immune cells (Palikhe et al, 2017). Additionally, carriers of the rs868853T allele were found to have a lower susceptibility to Kawasaki disease in a southern Chinese population (Che et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease

Jiang

Wu²,

Liu³

et al. 2023

Front. Pharmacol.

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Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC−MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

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“…Many studies have found that variants of ABCC4 were associated with multiple disease susceptibilities. Palikhe et al found that the variants of ABCC4 (rs868853) were associated with airway inflammation in asthmatics [ 40 ], and Likanonsakul et al found that the ABCC4 4976C allele was associated with beta2-microglobulinuria in human immunodeficiency virus- (HIV-) infected patients in Thailand and showed that this difference may help identify patients at greater risk of developing tenofovir diisopropyl fumarate-induced kidney tubular dysfunction [ 41 ]. Variants of ABCC4 (rs9561778) showed a significant association with cyclophosphamide-induced adverse drug reactions in breast cancer patients [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

ABCC4 Variants Modify Susceptibility to Kawasaki Disease in a Southern Chinese Population

Che

Fang³

et al. 2018

Disease Markers

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A previous family-based linkage study revealed that Kawasaki disease (KD) was associated with variations of the ATP-binding cassette subfamily C member 4 (ABCC4) gene in most European populations. However, significant differences exist among ethnic populations in European and Chinese subjects; therefore, whether ABCC4 variants indicate susceptibility to KD in Chinese children is unclear. The purpose of this research was to evaluate correlations between ABCC4 gene polymorphisms and susceptibility to KD in a Southern Chinese population. We genotyped six polymorphisms (rs7986087, rs868853, rs3765534, rs1751034, rs3742106, and rs9561778) in 775 KD patients and 774 healthy controls. Ninety-five percent confidence intervals (95% CIs) and odds ratios (ORs) were used to assess the strength of each association. We found that the rs7986087 T variant genotype was associated with significantly higher susceptibility to KD (adjusted OR = 1.30, 95% CI = 1.05–1.60 for rs7986087 CT/TT). However, the rs868853 T variant genotype was associated with significantly lower susceptibility to KD (adjusted OR = 0.74, 95% CI = 0.59–0.92 for rs868853 CT/CC). Compared with the patients with 0–4 ABCC4 risk genotypes, the patients with 5-6 ABCC4 risk genotypes had a significantly increased risk of KD (adjusted OR = 1.63, 95% CI = 1.07–2.47), and this risk was more significant in the subgroups of females, subjects aged 12–60 months, and individuals with coronary artery lesions. These results indicate that specific single-nucleotide polymorphisms in the ABCC4 gene may increase susceptibility to KD in a Southern Chinese population.

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A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

Cited by 8 publications

References 38 publications

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease

ABCC4 Variants Modify Susceptibility to Kawasaki Disease in a Southern Chinese Population

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