TY - JOUR
T1 - Transcriptome responses in blood reveal distinct biological pathways associated with arsenic exposure through drinking water in rural settings of Punjab, Pakistan
AU - Rehman, Muhammad Yasir Abdur
AU - van Herwijnen, Marcel
AU - Krauskopf, Julian
AU - Farooqi, Abida
AU - Kleinjans, Jos C. S.
AU - Malik, Riffat Naseem
AU - Briede, Jacco Jan
N1 - Funding Information:
We are thankful to the participants of current study for cooperation in providing biological samples. We acknowledge the Higher Education Commission (HEC) Pakistan in providing financial support to MYA Rehman under International Research Support Initiative Program (IRSIP) with grant number IRSIP-36-BMS-19 and Maastricht University, The Netherlands for providing funding for the analysis. We are thankful to Prof. Uzaira Rafique from FJWU, Rawalpindi Pakistan for assisting us in urinary As measurements. Authors also acknowledge Dr. Ahsan ul Haq from department of pharmacy, Dr. Umar Masood Quraishi from department of Plant Sciences, and Usman Ali from department of Environmental Sciences, Quaid-i-Azam University Islamabad for their assistance.
Funding Information:
We are thankful to the participants of current study for cooperation in providing biological samples. We acknowledge the Higher Education Commission (HEC) Pakistan in providing financial support to MYA Rehman under International Research Support Initiative Program (IRSIP) with grant number IRSIP-36-BMS-19 and Maastricht University , The Netherlands for providing funding for the analysis. We are thankful to Prof. Uzaira Rafique from FJWU, Rawalpindi Pakistan for assisting us in urinary As measurements. Authors also acknowledge Dr. Ahsan ul Haq from department of pharmacy, Dr. Umar Masood Quraishi from department of Plant Sciences, and Usman Ali from department of Environmental Sciences, Quaid-i-Azam University Islamabad for their assistance. Appendix A
Publisher Copyright:
© 2019
PY - 2020/2
Y1 - 2020/2
N2 - Background: Groundwater Arsenic (As) contamination is a global public health concern responsible for various health implications and a neglected area of environmental health research in Pakistan. Because of inter-individual differences in genetic predisposition, As-related health issues may not be equally distributed among the As-exposed population. However, fill date, no studies have been conducted including multiple SNPs involved in As metabolism and disease risk using a linear mixed effect model approach to analyze peripheral blood transcriptomics results.Objectives: In order to detect early responses on the gene expression level and to evaluate the impact of selected SNPs inferring disease risks associated with As exposure, we designed a systematic study to investigate blood transcriptomics profiles of 57 differentially exposed rural subjects living in drinking water As-contaminated settings of Lahore and Kasur districts in Punjab Province in southeast Pakistan. Exposure among the subjects was correlated with individual transcriptome responses applying urinary As profiles as the main biomarker for risk stratification.Methods: We performed whole genome gene expression analysis in blood of subjects using microarrays. Linear effect mixed models were applied for evaluating the combined impact of SNPs hypothetically increasing the risk for As exposure-induced health effects (GSTM1, GSTT1, As3MT, DNMT1, MTHFR, ERCC2 and EGFR).Results: Our findings confirmed important signaling, growth factor, cancer and other disease related pathways known to be associated with increased As exposure levels. In addition, upon implementing our integrative SNPs-based genetic risk factor, pathways associated with an increased risk of NAFLD and diabetes appeared significantly enhanced by down-regulation of genes NDUFV3, IKBKB, IL6R, ADIPOR1, PPARA, OGT and FOXO1.Conclusion: We report the first comprehensive study applying state-of-the-art bioinformatics approaches to address multiple SNP-based inter-individual variability in adverse molecular responses among subjects exposed to drinking water As contamination in Pakistan thereby providing strong evidence of various gene expression targets associated with development of known As-related diseases.
AB - Background: Groundwater Arsenic (As) contamination is a global public health concern responsible for various health implications and a neglected area of environmental health research in Pakistan. Because of inter-individual differences in genetic predisposition, As-related health issues may not be equally distributed among the As-exposed population. However, fill date, no studies have been conducted including multiple SNPs involved in As metabolism and disease risk using a linear mixed effect model approach to analyze peripheral blood transcriptomics results.Objectives: In order to detect early responses on the gene expression level and to evaluate the impact of selected SNPs inferring disease risks associated with As exposure, we designed a systematic study to investigate blood transcriptomics profiles of 57 differentially exposed rural subjects living in drinking water As-contaminated settings of Lahore and Kasur districts in Punjab Province in southeast Pakistan. Exposure among the subjects was correlated with individual transcriptome responses applying urinary As profiles as the main biomarker for risk stratification.Methods: We performed whole genome gene expression analysis in blood of subjects using microarrays. Linear effect mixed models were applied for evaluating the combined impact of SNPs hypothetically increasing the risk for As exposure-induced health effects (GSTM1, GSTT1, As3MT, DNMT1, MTHFR, ERCC2 and EGFR).Results: Our findings confirmed important signaling, growth factor, cancer and other disease related pathways known to be associated with increased As exposure levels. In addition, upon implementing our integrative SNPs-based genetic risk factor, pathways associated with an increased risk of NAFLD and diabetes appeared significantly enhanced by down-regulation of genes NDUFV3, IKBKB, IL6R, ADIPOR1, PPARA, OGT and FOXO1.Conclusion: We report the first comprehensive study applying state-of-the-art bioinformatics approaches to address multiple SNP-based inter-individual variability in adverse molecular responses among subjects exposed to drinking water As contamination in Pakistan thereby providing strong evidence of various gene expression targets associated with development of known As-related diseases.
KW - Arsenic
KW - Drinking water
KW - Health
KW - Pathways
KW - Transcriptomics
KW - Pakistan
KW - GENE-EXPRESSION PROFILES
KW - WIDE DNA METHYLATION
KW - FATTY LIVER-DISEASE
KW - VITAMIN-D-RECEPTOR
KW - EPIGENETIC MECHANISMS
KW - DIABETES-MELLITUS
KW - WEST-BENGAL
KW - CONTAMINATED GROUNDWATER
KW - DOWN-REGULATION
KW - SKIN-LESIONS
U2 - 10.1016/j.envint.2019.105403
DO - 10.1016/j.envint.2019.105403
M3 - Article
C2 - 31864032
SN - 0160-4120
VL - 135
JO - Environment International
JF - Environment International
M1 - 105403
ER -