The relationship between selected VDR, HFE and ALAD gene polymorphisms and several basic toxicological parameters among persons occupationally exposed to lead Anna Szyma  nska-Chabowska a , Lukasz Laczma  nski b , Iwona Je ˛drychowska a , Mariusz Chabowski c , Pawel Ga  c a, d , Agnieszka Janus a , Katarzyna Goslawska a , Beata Smyk a , Urszula Solska a , Grzegorz Mazur a , Rafal Pore ˛ba a, * a Department of Internal Medicine, Occupational Diseases and Hypertension, Wroclaw Medical University, Borowska 213, PL 50-556 Wroclaw, Poland b Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw Medical University, Pasteura 4, PL 50-367 Wroclaw, Poland c Clinic of Surgery, 4th Military Hospital, Weigla 5, PL 50-981 Wroclaw, Poland d Department of Radiology and Diagnostic Imaging, 4th Military Hospital, Weigla 5, PL 50-981 Wroclaw, Poland A R T I C L E I N F O Article history: Received 19 March 2015 Received in revised form 4 May 2015 Accepted 6 May 2015 Available online 8 May 2015 Keywords: Occupationally exposure Lead Gene polymorphisms A B S T R A C T The aim of this study was to find a relationship between polymorphisms of ALAD rs1805313, rs222808, rs1139488, VDR FokI and HFE C282Y and H63D and basic toxicological parameters (lead and ZnPP blood concentration) in people occupationally exposed to lead. We collected data of 101 workers (age 25– 63 years) directly exposed to lead. The toxicological lab tests included blood lead, cadmium and ZnPP concentration measurement and arsenic urine concentration measurement. Workers were genotyped for ALAD (rs1805313, rs222808, rs1139488), HFE (C282Y, H63D) and VDR (FokI). Individuals with the lead exposure and coexisting F allel in the locus Fok-I of VDR gene are suspected of higher zinc protoporphyrins concentrations. Workers exposed to the lead with the Y allel in the locus C282Y of the HFE gene are predisposed to lower ZnPP levels and individuals with coexisting H allel in the locus H63D HFE gene are predisposed to lower Pb-B levels. The T allel in the locus rs1805313 of the ALAD gene determines lower Pb-B and ZnPP levels in lead–exposed individuals. The heterozigosity of the locus rs2228083 of the ALAD gene has a strong predilection to higher Pb-B levels. The carriage of the C allel in the locus rs1139488 of the ALAD gene might determine higher Pb-B levels and the heterozigosity of the locus rs1139488 of the ALAD gene might result in higher ZnPP levels. Conclusion. The study revealed relationship between VDR, HFE and ALAD genes polymorphism and basic toxicological parameters in occupationally exposed workers. ã2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Lead has been recognized as a major heavy metal pollutant in some areas because of its wide distribution in the human environment (Lee et al., 2012). Lead is found at low concentrations in the earth’s crust, predominantly as lead sulfide, but the widespread occurrence of lead in the environment is largely the result of anthropogenic activity (IARC, 2006). In Poland exposure to this metal in the environmental and occupational settings (specially in urban Upper and Lower Silesia region) seems to be a serious public health problem. Lead has a long half-life in the body and at high exposure levels it causes encephalopathy, kidney damage, anemia and impairment of reproductive and immune system (García-Lestón et al., 2012). Lead exposure may also induce hypertension and cardiovascular diseases in some individuals (Onalaya and Claudio, 2008; Tekin et al., 2012). One of its primary effects is hematotoxicity, specifically inhibition of heme synthesis. Lead inhibits three enzymes in the heme biosynthesis pathway: delta-aminolevulinic acid dehydratase (ALAD), coporphyrinogen oxidase and ferrochelatase (Lee et al., 2012; Tekin et al., 2012; Yang et al., 2012). The International Agency for Research on Cancer classified lead as possible human carcinogen (group 2B) and its inorganic compounds as probable human carcinogens (group 2A) (García- Lestón et al., 2012; Pawlas et al., 2014). Occupational exposure to lead is most often occurred in lead smelting, hydrometallurgical and pyrometallurgical processes (removal of silver, gold, arsenic, bismuth or zinc) and battery * Corresponding author. Tel.: +48 71 736 40 00; fax: +48 71 736 40 09. E-mail address: sogood@poczta.onet.pl (R. Pore ˛ba). http://dx.doi.org/10.1016/j.tox.2015.05.002 0300-483X/ ã 2015 Elsevier Ireland Ltd. All rights reserved. Toxicology 334 (2015) 12–21 Contents lists available at ScienceDirect Toxicology journal homepa ge: www.elsev ier.com/locate /toxicol