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      Increased risk of aspirin-induced gastric mucosal erosion in elderly Chinese men harboring SLCO1B1*1b/*1b while using aspirin and an ACEI or ARB concomitantly

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          Abstract

          Background

          It is well established that long-term use of aspirin can cause gastric mucosal injury. ACEIs and ARBs are inversely related to gastric ulcer development. This study aimed to evaluate the relationship between SLCO1B1 polymorphisms, which can affect ACEI and ARB transport, and gastric mucosal erosion in elderly male Chinese patients with cardiovascular disease who use aspirin.

          Methods

          Patients taking aspirin and an ACEI or ARB concomitantly who had undergone endoscopic screening for gastric erosion were analyzed for SLCO1B1 polymorphisms by a TaqMan assay.

          Results

          The frequency of the SLCO1B1*1b/*1b diplotype (42% vs. 24%; p = 0.002) was significantly higher in the gastric mucosal erosion group than in the control group. After adjustment for significant factors, SLCO1B1*1b/*1b (OR, 2.64; 95% CI, 1.59–4.17; p < 0.05) was found to be associated with gastric mucosal erosion in aspirin users.

          Conclusions

          The presence of the SLCO1B1*1b/*1b diplotype may be a risk factor for aspirin-induced gastric mucosal erosion in elderly Chinese men taking aspirin and an ACEI or ARB concomitantly.

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          Most cited references18

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          Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics.

          Jessica Mwinyi, Andreas Johne, Steffen Bauer … (2004)
          We compared the pharmacogenetic effects of OATP-C (organic anion transporting polypeptide C) *1a, *1b (A388G), and *5 (T521C) haplotypes on single-dose pharmacokinetics of pravastatin in white subjects. Thirty healthy white male subjects were grouped according to their OATP-C haplotype. Each group contained 10 individuals who were either homozygous or heterozygous carriers of the *1a, *1b, or *5 haplotype. After a single oral dose of 40 mg pravastatin, we analyzed kinetic parameters of pravastatin disposition. Values for the area under the plasma concentration-time curve from time 0 to 6 hours [AUC(0-6)] in *1a/*1a, *1a/*1b or *1b/*1b, and *1a/*5 individuals were 114.5 +/- 68.6 microg. L(-1). h, 74.8 +/- 35.6 microg. L(-1). h, and 163.0 +/- 64.6 microg. L(-1). h, respectively, with highly significant differences across all 3 study groups (P =.006) and between subjects carrying the *1b and *5 haplotype (P =.002). Strikingly, values of AUC(0-6) from the OATP-C *1b group were more than 60% lower than those derived from carriers of the wild-type OATP-C *1a haplotype, although this difference failed to reach statistical significance. However, the amount of pravastatin excreted into the urine from time 0 to 12 hours [Ae(0-12)] was significantly diminished in the OATP-C *1b haplotype group (1729 +/- 907 microg) compared with *1a wild-type control subjects (2974 +/- 1590 microg) (P =.049). There was a significant effect of tested OATP-C variant haplotypes on pravastatin disposition. Whereas *5 expression delayed the hepatocellular uptake of pravastatin, *1b expression seemed to accelerate OATP-C-dependent uptake of the drug.
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            Community-based screening for chronic kidney disease among populations older than 40 years in Beijing.

            Mei Wang, Shuyu Wang, Haiyan Wang … (2007)
            Chronic kidney disease (CKD) is a public health problem, while data from developing countries are limited. We sought to investigate the epidemiological features of kidney damage in metropolis-residing Chinese adults (>40 years old), and to determine the associated factors of CKD. Two thousand three hundred and fifty-three residents in one district of Beijing were interviewed and tested for albuminuria, reduced renal function, haematuria and pyuria. The associations between demographic characteristics, health characteristics and indicators of kidney damage were examined. Albuminuria was detected in 6.2% of subjects; reduced renal function was found in 5.2% of subjects; haematuria was found in 0.8% and non-infective pyuria was found in 0.09%. Approximately, 11.3% (95% confidence interval: 10.0-12.8%) of subjects had at least one indicator of kidney damage. The awareness rate of CKD was only 7.2%. Systolic blood pressure and diabetes were independently associated with albuminuria. Age, diastolic blood pressure, hypercholesteraemia, hypertriglyceridaemia and hyperuricaemia were independently associated with reduced renal function. This is the first report on the prevalence of CKD in a community-based population within a developing country, determined using protocols recommended by kidney disease improving global outcomes (KDIGO). The prevalence of CKD in our population was close to the levels observed in developed countries, and the spectrum of CKD and associated factors were similar to developed countries. Results from this study suggest that strategies aimed at an intervention of hypertension and other metabolic disorders might prove effective in controlling the pandemic of CKD in China, as well as other developing countries.
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              PharmGKB very important pharmacogene: SLCO1B1.

              Russ Altman, Connie Oshiro, Jeffrey T. Klein … (2010)
              Article 0 comments Cited 27 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Hongbin Liu:
                ORCID: http://orcid.org/0000-0001-5356-7682
                +86-010-66876349 , liuhb301@sina.com
                Journal
                Journal ID (nlm-ta): BMC Med Genet
                Journal ID (iso-abbrev): BMC Med. Genet
                Title: BMC Medical Genetics
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2350
                Publication date (Electronic): 14 November 2019
                Publication date PMC-release: 14 November 2019
                Publication date Collection: 2019
                Volume: 20
                Electronic Location Identifier: 183
                Affiliations
                [1 ]ISNI 0000 0001 2267 2324, GRID grid.488137.1, Medical School of Chinese PLA, ; Beijing, 100853 China
                [2 ]ISNI 0000 0004 1761 8894, GRID grid.414252.4, Department of Geriatric Cardiology, , National Clinical Research Center for Geriatric Diseases, the Second Medical Center of PLA General Hospital, ; 28 Fuxing Road, Beijing, 100853 China
                Author information
                http://orcid.org/0000-0001-5356-7682
                Article
                Publisher ID: 918
                DOI: 10.1186/s12881-019-0918-4
                PMC ID: 6857243
                PubMed ID: 31727004
                SO-VID: dd814d18-f69e-4c28-9168-8b4d8e0671a1
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 2 April 2019
                Date accepted : 1 November 2019
                Funding
                Funded by: National Key Research Program of China
                Award ID: 2017YFC0840100 and 2017YFC0840103
                Award Recipient :
                Funded by: the Central Health Care Fund
                Award ID: W2015ZD02
                Award Recipient :
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Genetics
                Keywords: single nucleotide polymorphism,aspirin,gastric mucosa erosion,slco1b1,pharmacogenomics
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: single nucleotide polymorphism, aspirin, gastric mucosa erosion, slco1b1, pharmacogenomics

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