Gene Expression Patterns of Environmental Chemicals in Human Cell Lines using HazChem Human Array
BIOCHIP JOURNAL
Authors: Park, Hye-Won; Kim, Seung-Jun; Oh, Moon-Ju; Youn, Jong-Pil; Ha, Jung-Mi; Paul, Saswati; Kim, Youn-Jung; Ryu, Jae-Chun; Hwang, Seung Yong
Abstract
The human HazChem array includes 16 control genes and 300 environmental toxicity-related genes. In past experiments, the expression levels of these genes were altered in whole genome microarray experiments using VOCs and PAH-treated human cells. In this study, we employed the human HazChem array to determine the gene expression pattern of chemical groups. The chemical groups used in this study were PAHs, POPs, and VOCs. PAHs are one of the most widespread organic pollutants. We used chrysene and phenanthrene as examples of PAHs. POPs are chemical substances that remain in the environment, and bioaccumulate through the food chain. We utilized chlordane and toxaphene as our sample POPs. VOCs are important outdoor air pollutants. They have been shown to cause nervous system disorders through respiration and skin contact, and generally are associated with foul odors. We utilized dichloromethane, ethylbenzene, and trichloroethylene as our sample VOCs. Thus, a total of 7 chemicals were assessed. In this study, HepG2 cells were treated with Polycyclic Aromatic Hydrocarbons (PAHs) and Persistent Organic Pollutants (POPs). HL-60 cells were treated with Volatile Organic Compounds (VOCs). Following comparative analysis, we detected some specific expression patterns in each of the chemical groups. We determined that the 7 chemicals utilized herein were divided into 3 chemical groups on the basis of the following 16 genes: HHEX, HLA-G, C1QBP, RHEBL1, PMAIP1, PHIP, HK2, NOTCH1, PRF1, SGK, PLK3, BGLAP, LOC389844, GDF15, NRF1 and ABCC2. Subsequently, the HazChem Human array was used to group the chemicals.
Replication of Type 2 Diabetes Candidate Genes Variations in Three Geographically Unrelated Indian Population Groups
PLOS ONE
Authors: Ali, Shafat; Chopra, Rupali; Manvati, Siddharth; Singh, Yoginder Pal; Kaul, Nabodita; Behura, Anita; Mahajan, Ankit; Sehajpal, Prabodh; Gupta, Subash; Dhar, Manoj K.; Chainy, Gagan B. N.; Bhanwer, Amarjit S.; Sharma, Swarkar; Bamezai, Rameshwar N. K.
Abstract
Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E204) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E208) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95% CI = 1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.