Do the MTHFR gene polymorphism and Down syndrome pregnancy association stands true? A case–control study of Indian population and meta-analysis

Background: Down syndrome, the most common trisomy 21 arises from abnormal chromosomal segregation. The etiology includes genetic and acquired factors. The main genetic factor that is well appreciated for onset of Down syndrome pregnancy is MTHFR gene polymorphism. But till date, no final conclusion has arrived despite multiple studies on this gene polymorphism.Aim: To investigate the risk of MTHFR gene polymorphisms, C677T and A1298C, with Down syndrome pregnancies and a meta-analysis of published literature.Subjects and methodology: PCR-RFLP method was used to genotype C677T and A1298C polymorphism. For meta-analysis the literature was retrieved from PubMed database with the key words, MTHFR polymorphism; C677T; A1298C and Down syndrome.Results: Mothers carrying C677T polymorphism had a risk of 2.48 times compared with control subjects while A1298C polymorphism carriers had 1.60 times and 2.12 times increased risk under assumption of dominant and recessive model. However, meta-analysis of published studies resulted in 1.26 times and 1.32 times increased risk of Down syndrome pregnancies among the C677T carries under the assumption of recessive and dominant models of inheritance. Considering A1298C polymorphism, dominant model predicated no risk; recessive model resulted in 1.34 times increased risk in CC genotype individuals. In subgroup analysis, Indian studies had a risk of 1.61 times and 1.44 times under recessive and dominant model of C677T polymorphism inheritance while A1298C polymorphism carriers had a risk of 1.75 and 1.46 under the assumption of recessive and dominant inheritance.Conclusion: Our study suggests that both C677T and A1298C polymorphisms are significantly associated with the risk of DS pregnancy

Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases

ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors

Phase-based supervisory control for fermentation process development

10.1016/S0959-1524(02)00063-XJournal of Process Control135367-382JPCO

Identification of Novel Genomic Variations in Susceptibility to Nonsyndromic Cleft Lip and Palate Patients

Background: Nonsyndromic cleft lip with or without palate (NSCL/P) is a multifactorial and common birth malformation caused by genetic and environmental factors, as well as by teratogens. Genome-wide association studies found genetic variations with modulatory effects of NSCL/P formation in Chinese and Iranian populations. We aimed to identify the susceptibility of single-nucleotide polymorphisms (SNPs) to nonsyndromic cleft lip with or without palate in the Indian population. Material and Methods: The present study was conducted on NSCL/P cases and controls. Genomic DNA was extracted from peripheral blood and Axiom- Precision Medicine Research Array (PMRA) was performed. The Axiom-PMRA covers 902,527 markers and several thousand novel risk variants. Quality control-passed samples were included for candidate genetic variation identification, gene functional enrichment, and pathway and network analysis. Results: The genome-wide association study identified fourteen novel candidate gene SNPs that showed the most significant association with the risk of NSCL/P, and eight were predicted to have regulatory sequences. Conclusion: The GWAS study showed novel candidate genetic variations in NSCL/P formations. These findings contribute to the understanding of genetic predisposition to nonsyndromic cleft lip with or without palate

Transcriptional regulation of cytokines and oxidative stress by gallic acid in human THP-1 monocytes

Increased inflammation/prooxidation has been linked not only to Type 2 diabetes but also in prediabetes state. In this study we investigated hyperglycemia-mediated proinflammatory/prooxidant effects in THP-1 monocytes and tested whether gallic acid could attenuate changes in gene expression induced by high-glucose. Cells were treated either with 5.5 mM glucose or 25 mM glucose in the absence and presence of gallic acid. While oxidative DNA damage was assessed by COMET assay, GSH and GSSG levels were estimated fluorimetrically. Gene expression patterns were determined by RT-PCR. Cells treated with high-glucose showed increased DNA damage and glutathione depletion and this was attenuated in the presence of gallic acid. High-glucose treated cells exhibited increased mRNA expression of TNF-α, IL-6, NADPH oxidase and TXNIP and gallic acid attenuated these proinflammatory and prooxidant effects. Cells treated with high-glucose revealed a deficiency in mounting SOCS-3 expression and gallic acid upregulates this feedback regulatory signal. Gallic acid attenuates DNA damage, maintains glutathione turnover, and suppresses hyperglycemia-induced activation of proinflammatory and prooxidant gene expression. Gallic acid beneficially modulate transcription of functionally diverse groups of genes and its regulation of SOCS-3 and TXNIP signals is a newly identified mechanism that has therapeutic implications