D. Kaya-Akyüzlü

Association between delta-aminolevulinic acid dehydratase polymorphism and placental lead levels.

Lead inhibits the delta-aminolevulinic acid dehydratase (ALAD) activity and results in neurotoxic aminolevulinic acid accumulation in the blood. During pregnancy, lead in the maternal blood can easily cross the placenta. The aim of this study was to determine whether the maternal ALAD G177C polymorphism (rs1800435) was related to the placental lead levels. The study population comprised 97 blood samples taken from mothers to investigate ALAD G177C polymorphism and their placentas to measure lead levels. ALAD G177C polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique and atomic absorption spectrometry (AAS) equipped with a graphite furnace and Zeeman background correction system was used for lead determination. The median placental lead levels for ALAD1-1, ALAD1-2 and ALAD2-2 genotypes were 7.54 μg/kg, 11.78 μg/kg and 18.53 μg/kg, respectively. Statistically significant association was found between the maternal ALAD G177C polymorphism and placental lead levels (p<0.05). This study suggested that maternal ALAD G177C polymorphism was associated with placental lead levels.

Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother-placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR-RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborns placentas and umbilical cord bloods.

Does maternal VDR FokI single nucleotide polymorphism have an effect on lead levels of placenta, maternal and cord bloods?

INTRODUCTION Individual susceptibility due to genetic variations appears to be an important factor in lead toxicity. As lead, ubiquitous atmospheric pollutant, behaves very similarly to calcium, gene polymorphisms in proteins involved in calcium homeostasis can affect lead toxicokinetics. Vitamin D receptor (VDR), a DNA-binding transcription factor, activates genes that encode proteins involved in calcium metabolism. Thus, the objective of this study was to determine the effect of maternal VDR FokI polymorphism on lead levels of maternal blood, placental tissue and cord blood. METHODS The study population comprised 116 women and their respective placenta and umbilical cord. Venous blood samples were drawn from mothers to investigate both the lead levels and VDR FokI polymorphism. Cord blood samples and placentas were collected for lead levels. VDR FokI polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Lead levels were analyzed by dual atomic absorption spectrometer system. RESULTS Genotype frequencies of VDR FokI polymorphism were 49.2% FF, 44.8% Ff and 6.0% ff. The mean lead levels of maternal blood, placenta and cord blood were 36.76 ± 13.84 μg/L, 12.84 ± 14.47 μg/kg and 25.69 ± 11.12 μg/L, respectively. Maternal blood, placental and cord blood lead levels were found significantly to be higher in mothers with f allele for the VDR FokI polymorphism (p < 0.05). DISCUSSION The present study indicated that this polymorphism had an effect on maternal and fetal lead levels and that mothers with F allele associated with lower lead concentration may protect their respective fetus against the toxic effects of lead exposure.

Influence of MRP1 G1666A and GSTP1 Ile105Val genetic variants on the urinary and blood arsenic levels of Turkish smelter workers

To understand the cellular mechanisms responsible for arsenic metabolism and transport pathways plays a fundamental role in order to prevent the arsenic-induced toxicity. The effect of MRP1 G1666A and GSTP1 Ile105Val polymorphisms on blood and urinary arsenic levels were determined in 95 Turkish smelter workers. Blood and urinary arsenic concentrations were measured by GF-AAS with Zeeman correction and gene polymorphisms were investigated by PCR-RFLP method. The mean blood and urinary arsenic levels were 21.60±12.28μg/L and 5.58±4.37μg/L, respectively. A significant association between MRP1 1666A allele and urinary arsenic levels was found (p=0.001). GSTP1 Ile105Val polymorphism was detected not to be associated with either blood or urinary arsenic levels (p=0.384, p=0.440, respectively). Significant association was also detected between MRP1A(-)/GSTP1Val(-) genotypes and urinary arsenic levels (p=0.001). This study suggested that MRP1 G1666A alone and, also, combined with GSTP1 Ile105Val were associated with inter-individual variations in urinary arsenic levels, but not with blood arsenic levels.

Evaluation of Relationship Between Lymphocyte DNA Damages and Blood Arsenic Levels in Silver Mining Workers using Alkaline Comet Assay

Bu calismadaki amac, mesleki arsenige maruz bireylerde kan arsenik (As) duzeyi ve DNA hasar arasindaki iliskiyi arastirmaktir. Gumus madeni iscilerinden 120 bireyin lenfositlerindeki DNA hasari comet yontemi (tek hucre jel elektroforezi) kullanilarak belirlendi. DNA hasar duzeyleri BAB Bs Comet Assay sistemi ile hesaplandi ve As duzeyleri atomic absorbsiyon spektroskopi (AAS) cihazi ile analiz edildi. Kan As duzeyi ortalamasi 17.03±10.85 μg/L olarak tespit edildi. Kan As ve comet parametreleri (kuyruk yogunlugu, comet uzunlugu ve kuyruk uzunlugu) arasinda istatistiksel olarak anlamli pozitif korelasyon bulundu (sirasiyla; r=0.360, r=0.334, r=0.259; p<0.01). Sonuclarimiz, Turk Eti Maden gumus iscilerinde arsenik maruziyetinin periferik lenfosit DNA hasarina sebep oldugunu gosterdi.