Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene ( VDR) May Have an Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations of AP Patients and Alcohol-Abuse Controls

Anna Cieślińska, Elżbieta Kostyra, Ewa Fiedorowicz, Jadwiga Snarska, Natalia Kordulewska, Krzysztof Kiper, Huub F J Savelkoul, Anna Cieślińska, Elżbieta Kostyra, Ewa Fiedorowicz, Jadwiga Snarska, Natalia Kordulewska, Krzysztof Kiper, Huub F J Savelkoul

Abstract

Vitamin D imbalance is suggested to be associated with the development of pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but not yet in pancreatitis. The aim of this study was to explore possible associations of the four SNPs in the VDR receptor gene in a population of acute pancreatitis patients and alcohol-abuse controls, and to investigate the association with acute pancreatitis (AP) susceptibility. The study population (n = 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse control group (n = 110). All patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI: 1.68⁻4.03; p < 0.0001) to be almost three times more frequent in the AP group compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in the vitamin D receptor may have an impact on the development of acute pancreatitis due to the lack of the protective role of vitamin D.

Keywords: SNP analysis; acute pancreatitis; polymorphism; vitamin D; vitamin D receptor.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

References

    1. Weiss F.U., Simon P., Mayerle J., Kraft M., Lerch M.M. Germline mutations and gene polymorphism associated with human pancreatitis. Endocrinol. Metab. Clin. N. Am. 2006;35:289–302. doi: 10.1016/j.ecl.2006.02.001.
    1. Nieminen A., Maksimow M., Mentula P., Kyhälä L., Kylänpää L., Puolakkainen P., Salmi M. Circulating cytokines in predicting development of severe acute pancreatitis. Crit. Care. 2014;18:R104. doi: 10.1186/cc13885.
    1. Wojtuń S., Gil J., Błaszak A. Dietary treatment in acute pancreatitis. Pol. Merkur. Lekarski. 2007;22:469–473.
    1. Lankisch P.G., Apte M., Banks P.A. Acute pancreatitis. Lancet. 2015;4:85–96. doi: 10.1016/S0140-6736(14)60649-8.
    1. Yadav D., Vege S.S., Chari S.T. GI Epidemiology: Diseases and Clinical Methodology. 2nd ed. Wiley Blackwell; Oxford, UK: 2014. Epidemiology of Pancreatitis; pp. 306–312.
    1. Eyles D.W., Smith S., Kinobe R., Hewison M., McGrath J.J. Distribution of the vitamin D receptor and 1α-hydroxylase in human brain. J. Chem. Neuroanat. 2005;29:21–30. doi: 10.1016/j.jchemneu.2004.08.006.
    1. Eyles D.W., Burne T.H., McGrath J.J. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front. Neuroendocrinol. 2013;34:47–64. doi: 10.1016/j.yfrne.2012.07.001.
    1. Anglin R.E., Samaan Z., Walter S.D., McDonald S.D. Vitamin D deficiency and depression in adults: Systematic review and meta-analysis. Br. J. Psychiatry. 2013;202:100–107. doi: 10.1192/bjp.bp.111.106666.
    1. Raimondi S., Maisonneuve P., Lowenfels A.B. Epidemiology of pancreatic cancer: An overview. Nat. Rev. Gastroenterol. Hepatol. 2009;6:699. doi: 10.1038/nrgastro.2009.177.
    1. Bhimani M.M. Vitamin D: Does it play a role in psychiatry. J. Pak. Med. Assoc. 2012;62:181.
    1. Wagnerberger S., Kanuri G., Bergheim I. Trends in Alcoholic Liver Disease Research-Clinical and Scientific Aspects. InTech; Rijeka, Croatia: 2012. Alcohol drinking patterns and nutrition in alcoholic liver disease; pp. 1–22.
    1. Neupane S.P., Lien L., Hilberg T., Bramness J.G. Vitamin D deficiency in alcohol-use disorders and its relationship to comorbid major depression: A cross-sectional study of inpatients in Nepal. Drug Alcohol. Depend. 2013;133:480–485. doi: 10.1016/j.drugalcdep.2013.07.006.
    1. Lieber C.S. Alcohol: Its metabolism and interaction with nutrients. Annu. Rev. Nutr. 2000;20:395–430. doi: 10.1146/annurev.nutr.20.1.395.
    1. Kim D.I., Kim H., Son P., Kang J.H., Kang B.T., Yang M.P. Serum 25-hydroxyvitamin D concentrations in dogs with suspected acute pancreatitis. J. Vet. Med. Sci. 2017;79:1366–1373. doi: 10.1292/jvms.16-0647.
    1. Holick M.F. Vitamin D deficiency. N. Engl. J. Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Haussler M.R., Whitfield G.K., Haussler C.A., Hsieh J.C., Thompson P.D., Selznick S.H., Jurutka P.W. The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J. Bone Miner. Res. 1998;13:325–349. doi: 10.1359/jbmr.1998.13.3.325.
    1. Mehta R.G., Mehta R.R. Vitamin D and cancer. J. Nutr. Biochem. 2002;13:252–264. doi: 10.1016/S0955-2863(02)00183-3.
    1. Mathieu C., van Etten E., Decallonne B., Guilietti A., Gysemans C., Bouillon R., Overbergh L. Vitamin D and 1, 25-dihydroxyvitamin D3 as modulators in the immune system. J. Steroid Biochem. Mol. Biol. 2004;89:449–452. doi: 10.1016/j.jsbmb.2004.03.014.
    1. Valdivielso J.M., Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin. Chim. Acta. 2006;371:1–12. doi: 10.1016/j.cca.2006.02.016.
    1. Sayeed I., Stein D.G. Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog. Brain Res. 2009;175:219–237. doi: 10.1016/S0079-6123(09)17515-5.
    1. Ramagopalan S.V., Heger A., Berlanga A.J., Maugeri N.J., Lincoln M.R., Burrell A., Watson C.T. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res. 2010;20:1352–1360. doi: 10.1101/gr.107920.110.
    1. Sigmundsdottir H. From the bench to the clinic: New aspects on immunoregulation by vitamin D analogs. Dermatoendocrinology. 2011;3:187–192. doi: 10.4161/derm.15115.
    1. Harms L.R., Burne T.H., Eyles D.W., McGrath J.J. Vitamin D and the brain. Best Pract. Res. Clin. Endocrinol. Metab. 2011;25:657–669. doi: 10.1016/j.beem.2011.05.009.
    1. Johnson J.D., Kuang S., Misler S., Polonsky K.S. Ryanodine receptors in human pancreatic β cells: Localization and effects on insulin secretion. FASEB J. 2004;18:878–880. doi: 10.1096/fj.03-1280fje.
    1. Zaki M., Kamal S., Basha W.A., Youness E., Ezzat W., El-Bassyouni H., Amr K. Association of vitamin D receptor gene polymorphism (VDR) with vitamin D deficiency, metabolic and inflammatory markers in Egyptian obese women. Genes Dis. 2017;4:176–182. doi: 10.1016/j.gendis.2017.07.002.
    1. Ishida H., Norman A.W. Demonstration of a high affinity receptor for 1, 25-dihydroxyvitamin D3 in rat pancreas. Mol. Cell. Endocrinol. 1988;60:109–117. doi: 10.1016/0303-7207(88)90169-4.
    1. Johnson J.A., Grande J.P., Roche P.C., Kumar R. Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. Am. J. Physiol. 1994;267:E356–E360. doi: 10.1152/ajpendo.1994.267.3.E356.
    1. Faraco J.H., Morrison N.A., Baker A., Shine J., Frossard P.M. ApaI dimorphism at the human vitamin D receptor gene locus. Nucleic Acids Res. 1989;17:2150. doi: 10.1093/nar/17.5.2150.
    1. Morrison N.A., Yeoman R., Kelly P.J., Eisman J.A. Contribution of trans-acting factor alleles to normal physiological variability: Vitamin D receptor gene polymorphism and circulating osteocalcin. Proc. Natl. Acad. Sci. USA. 1992;89:6665–6669. doi: 10.1073/pnas.89.15.6665.
    1. Morrison N.A., Qi J.C., Tokita A., Kelly P.J., Crofts L., Nguyen T.V., Eisman J.A. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–287. doi: 10.1038/367284a0.
    1. Saijo T., Ito M., Takeda E., Huq A.H., Naito E., Yokota I., Kuroda Y. A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: Utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am. J. Hum. Genet. 1991;49:668.
    1. Gross C., Eccleshall T.R., Malloy P.J., Villa M.L., Marcus R., Feldman D. The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in postmenopausal Mexican-American women. J. Bone Miner. Res. 1996;11:1850–1855. doi: 10.1002/jbmr.5650111204.
    1. Uitterlinden A.G., Fang Y., van Meurs J.B., van Leeuwen H., Pols H.A. Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J. Steroid Biochem. Mol. Biol. 2004;89:187–193. doi: 10.1016/j.jsbmb.2004.03.083.
    1. Cieślińska A., Kostyra E., Chwała B., Moszyńska-Dumara M., Fiedorowicz E., Teodorowicz M., Savelkoul H.F. Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism. Brain Sci. 2017;7:115. doi: 10.3390/brainsci7090115.
    1. Whitcomb D.C. Genetic risk factors for pancreatic disorders. Gastroenterology. 2013;144:1292–1302. doi: 10.1053/j.gastro.2013.01.069.
    1. Tardelli V.S., do Lago M.P.P., da Silveira D.X., Fidalgo T.M. Vitamin D and alcohol: A review of the current literature. Psychiatry Res. 2017;248:83–86. doi: 10.1016/j.psychres.2016.10.051.
    1. Ogunsakin O., Hottor T., Mehta A., Lichtveld M., McCaskill M. Chronic ethanol exposure effects on vitamin D levels among subjects with alcohol use disorder. Environ. Health Insights. 2016;10:EHI-S40335. doi: 10.4137/EHI.S40335.
    1. Becker K.G. Autism, immune dysfunction and Vitamin D. Acta Psychiatr. Scand. 2011;124:74. doi: 10.1111/j.1600-0447.2011.01688.x.
    1. Eyles D., Burne T., McGrath J. Vitamin D in fetal brain development. Semin. Cell Dev. Biol. 2011;22:629–636. doi: 10.1016/j.semcdb.2011.05.004.
    1. Forouhi N.G., Luan J.A., Cooper A., Boucher B.J., Wareham N.J. Baseline serum 25-hydroxy vitamin D is predictive of future glycemic status and insulin resistance: The Medical Research Council Ely Prospective Study 1990–2000. Diabetes. 2008;57:2619–2625. doi: 10.2337/db08-0593.
    1. Knekt P., Laaksonen M., Mattila C., Härkänen T., Marniemi J., Heliövaara M., Reunanen A. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–671. doi: 10.1097/EDE.0b013e318176b8ad.
    1. Dobrian A.D., Ma Q., Lindsay J.W., Leone K.A., Ma K., Coben J., Nadler J.L. Dipeptidyl peptidase IV inhibitor sitagliptin reduces local inflammation in adipose tissue and in pancreatic islets of obese mice. Am. J. Physiol. Endocrinol. Metab. 2010;300:E410–E421. doi: 10.1152/ajpendo.00463.2010.
    1. Zhao H., Wei R., Wang L., Tian Q., Tao M., Ke J., Hong T. Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner. Am. J. Physiol. Endocrinol. Metab. 2014;306:E1431–E1441. doi: 10.1152/ajpendo.00017.2014.
    1. Chiu K.C., Chu A., Go V.L.W., Saad M.F. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am. J. Clin. Nutr. 2004;79:820–825. doi: 10.1093/ajcn/79.5.820.
    1. Hewison M., Gacad M.A., Lemire J., Adams J.S. Vitamin D as a cytokine and hematopoetic factor. Rev. Endocr. Metab. Disord. 2001;2:217–227. doi: 10.1023/A:1010015013211.
    1. Palomer X., González-Clemente J.M., Blanco-Vaca F., Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes. Metab. 2008;10:185–197. doi: 10.1111/j.1463-1326.2007.00710.x.
    1. Garcion E., Wion-Barbot N., Montero-Menei C.N., Berger F., Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol. Metab. 2002;13:100–105. doi: 10.1016/S1043-2760(01)00547-1.
    1. Berk M., Jacka F.N., Williams L.J., Ng F., Dodd S., Pasco J.A. Is this D vitamin to worry about? Vitamin D insufficiency in an inpatient sample. Aust. N. Z. J. Psychiatry. 2008;42:874–878. doi: 10.1080/00048670802345516.
    1. Sweiry J.H., Mann G.E. Role of oxidative stress in the pathogenesis of acute pancreatitis. Scand. J. Gastroenterol. Suppl. 1996;31:10–15. doi: 10.3109/00365529609104992.
    1. Tsai K., Wang S.S., Chen T.S., Kong C.W., Chang F.Y., Lee S.D., Lu F.J. Oxidative stress: An important phenomenon with pathogenetic significance in the progression of acute pancreatitis. Gut. 1998;42:850–855. doi: 10.1136/gut.42.6.850.
    1. Wang Y., Zhu J., DeLuca H.F. Where is the vitamin D receptor? Arch. Biochem. Biophys. 2012;523:123–133. doi: 10.1016/j.abb.2012.04.001.
    1. Brożyna A.A., Jóźwicki W., Slominski A.T. Decreased VDR expression in cutaneous melanomas as marker of tumor progression: New data and analyses. Anticancer Res. 2014;34:2735–2743.
    1. Jóźwicki W., Brożyna A.A., Siekiera J., Slominski A.T. Expression of vitamin D receptor (VDR) positively correlates with survival of urothelial bladder cancer patients. Int. J. Mol. Sci. 2015;16:24369–24386. doi: 10.3390/ijms161024369.
    1. Agliardi C., Guerini F.R., Saresella M., Caputo D., Leone M.A., Zanzottera M., Al-Daghri N. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1* 15-positive individuals. Brain Behav. Immun. 2011;25:1460–1467. doi: 10.1016/j.bbi.2011.05.015.
    1. Oh J., Weng S., Felton S.K., Bhandare S., Riek A., Butler B., Bernal-Mizrachi L. 1,25(OH)2 vitamin D inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation. 2009;120:687–698. doi: 10.1161/CIRCULATIONAHA.109.856070.
    1. Al-Daghri N.M., Guerini F.R., Al-Attas O.S., Alokail M.S., Alkharfy K.M., Draz H.M., Biasin M. Vitamin D receptor gene polymorphisms are associated with obesity and inflammosome activity. PLoS ONE. 2014;9:e102141. doi: 10.1371/journal.pone.0102141.
    1. Poon A.H., Laprise C., Lemire M., Montpetit A., Sinnett D., Schurr E., Hudson T.J. Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am. J. Respir. Crit. Care Med. 2004;170:967–973. doi: 10.1164/rccm.200403-412OC.
    1. Raby B.A., Lazarus R., Silverman E.K., Lake S., Lange C., Wjst M., Weiss S.T. Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am. J. Respir. Crit. Care Med. 2004;170:1057–1065. doi: 10.1164/rccm.200404-447OC.
    1. Kim J.S., Kim Y.I., Song C., Yoon I., Park J.W., Choi Y.B., Lee K.S. Association of vitamin D receptor gene polymorphism and Parkinson’s disease in Koreans. J. Korean Med. Sci. 2005;20:495–498. doi: 10.3346/jkms.2005.20.3.495.
    1. Saadi A., Gao G., Li H., Wei C., Gong Y., Liu Q. Association study between vitamin D receptor gene polymorphisms and asthma in the Chinese Han population: A case-control study. BMC Med. Genet. 2009;10:71. doi: 10.1186/1471-2350-10-71.
    1. Knekt P., Kilkkinen A., Rissanen H., Marniemi J., Sääksjärvi K., Heliövaara M. Serum vitamin D and the risk of Parkinson disease. Arch. Neurol. 2010;67:808–811. doi: 10.1001/archneurol.2010.120.
    1. Heine G., Hoefer N., Franke A., Nöthling U., Schumann R.R., Hamann L., Worm M. Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults. Br. J. Dermatol. 2013;168:855–858. doi: 10.1111/bjd.12077.
    1. Maalmi H., Sassi F.H., Berraies A., Ammar J., Hamzaoui K., Hamzaoui A. Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children: A case control study. Hum. Immunol. 2013;74:234–240. doi: 10.1016/j.humimm.2012.11.005.
    1. Rahsaz M., Azarpira N., Nikeghbalian S., Geramizadeh B., Aghdaie M.H., Daraie M., Karimi M.H. Vitamin D receptor genotype in pancreas allograft: A pilot study. Exp. Clin. Transplant. 2012;10:487–491. doi: 10.6002/ect.2011.0115.
    1. Vimaleswaran K.S., Cavadino A., Berry D.J., Mangino M., Andrews P., Moore J.H., Hyppönen E. Interaction between allelic variations in vitamin D receptor and retinoid X receptor genes on metabolic traits. BMC Genet. 2014;15:37. doi: 10.1186/1471-2156-15-37.
    1. Pani M.A., Knapp M., Donner H., Braun J., Baur M.P., Usadel K.H., Badenhoop K. Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes. 2000;49:504–507. doi: 10.2337/diabetes.49.3.504.
    1. Maalmi H., Berraïes A., Tangour E., Ammar J., Abid H., Hamzaoui K., Hamzaoui A. The impact of vitamin D deficiency on immune T cells in asthmatic children: A case-control study. J. Asthma Allergy. 2012;5:11. doi: 10.2147/JAA.S29566.

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