Md. Mustafa

Intra uterine growth retardation: Association with organochlorine pesticide residue levels and oxidative stress markers

Intra uterine growth retardation (IUGR) is a major complication of pregnancy, affecting ∼5% to 10% of newborns. Hexachlorocyclohexane (HCH) is an organochlorine pesticide that consists of eight stereoisomers and γ-isomer is the only isomer that possesses insecticidal activity. The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and to assess the level of oxidative stress markers as well as to establish correlation with OCP levels. Fifty women delivering neonates with low birth weight (IUGR) and equal number of women delivering normal birth weight babies (control) were recruited. We have observed higher levels of γ-HCH and T-HCH and increased oxidative stress markers in IUGR subjects versus control subjects. Significant correlations were also found between HCH isomers and oxidative stress markers in IUGR subjects. In conclusion, our results suggest that higher levels of HCH isomers may be associated with IUGR and increased oxidative stress.

Association between recurrent miscarriages and organochlorine pesticide levels.

OBJECTIVES Recurrent miscarriage (RM) is a challenging medical problem because of its unknown pathogenesis and etiology in most of the cases. Recent studies suggest the role of persistent environmental pollutants such as organochlorine pesticides (OCPs) in the etiology of RM. The present study was conducted to investigate possible associations of OCPs in the pathogenesis of RM. DESIGN AND METHODS Blood OCP levels were analyzed in women with RM (cases) and women with normal full term delivery with live birth (controls) by using a gas chromatograph equipped with an electron capture detector. RESULTS A statistically significant association (p=0.01) was observed between blood gamma-HCH levels and women with recurrent miscarriages. CONCLUSIONS This study suggests that high blood levels of gamma-HCH may be associated with risk of RM.

A preliminary study on the influence of glutathione S transferase T1 (GSTT1) as a risk factor for late onset Alzheimer's disease in North Indian population

INTRODUCTION Oxidative stress plays key role in pathogenesis of Alzheimers disease. Glutathione S-transferases (GSTs), a family of phase-II isoenzymes, play a critical role in providing protection against electrophiles and products of oxidative stress. Among different classes of GSTs, GSTM1 (Mu) and GSTT1 (theta) are found to be genetically deleted which results in decreased expression of the concerned enzyme. This study aims at preliminary analysis of the frequency of deletion of GSTM1 and GSTT1 and their association with late-onset Alzheimers disease. MATERIAL AND METHODS In this study, association of the deletion type polymorphism of GST M1 and T1 as possible risk factors for dementia of Alzheimers type was studied in 50 patients and 100 controls. Dementia was diagnosed by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scale. Genotyping was done by multiplex Polymerase Chain Reaction (PCR). Associations between null genotype of either GSTM1 and GSTT1 or both with Alzheimers disease were analyzed by Chi-Square test. RESULTS Deletion of GSTT1 was found significantly associated with Alzheimers disease (χ(2)=5.08, p=0.02*). CONCLUSIONS The odds of Alzheimers disease in null GSTT1 is found to be increased by 2.47 times in comparison to positive GSTT1.

CYP17A1 gene polymorphisms and environmental exposure to organochlorine pesticides contribute to the risk of small for gestational age

OBJECTIVES The cytochrome P-450c17α enzyme encoded by the cytochrome P-450c17α (CYP17A1) gene plays a role in oestrogen synthesis. Genetic variation in the maternal CYP17A1 gene leads to differences in oestrogen level that affect fetal growth and cause small for gestational age (SGA). Organochlorine pesticides (OCPs) are endocrine disruptors that alter the normal oestrogen-progesterone balance, and are associated with adverse reproductive outcomes. This study was designed to investigate the effect of the gene-environment interaction between maternal CYP17A1 gene polymorphisms and maternal and cord OCP levels on the risk of SGA. STUDY DESIGN Maternal and cord blood samples of 50 term SGA cases (birth weight <10th percentile for gestational age as per Lubchencos growth chart) and 50 normal pregnancies (controls) were collected. Women with occupational exposure to OCPs, anaemia, hypertension, antiphospholipid antibody syndrome, medical disease, parity of more than four, or a history of smoking, alcohol consumption or chronic drug intake were excluded from both groups. Maternal and cord blood samples were collected at the time of delivery or after delivery, respectively. The OCP levels of the samples were analyzed using a gas chromatography system equipped with an electron capture detector, and polymerase chain reaction-restriction fragment length polymorphism was used for polymorphic analysis of the CYP17A1 gene. RESULTS Significantly (p<0.05) higher levels of α-hexachlorocyclohexane (HCH), β-HCH and γ-HCH were found in maternal and cord blood samples of the SGA cases compared with the controls. The frequency of the A1A2/A2A2 genotype was significantly lower [p=0.041, odds ratio (OR) 0.421, 95% confidence interval (CI) 0.184-0.966] in the SGA cases compared with the controls. When gene-environment interactions between CYP17A1 gene polymorphisms and OCP levels were considered, a significant (p=0.004) association was found between a high level of endosulfan in cord blood and the A1A1 (wild-type) genotype of CYP17A1, leading to an estimated reduction in birth weight of 315g. CONCLUSIONS Higher OCP levels and the A1A1 genotype of CYP17A1 in pregnant women may be considered as important aetiological factors in idiopathic SGA. This study provides evidence that genetic variation and its interaction with environmental exposure may increase the risk of SGA. Further studies are needed with a larger sample size, incorporating other gene polymorphisms and environmental exposures, to strengthen these observations.

Genetic polymorphisms in Cytochrome P 4501B1 and susceptibility to idiopathic preterm labor in North Indian population.

OBJECTIVE The etiology of preterm labor (PTL) is still unknown, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We investigated the relation between PTL and polymorphisms in Cytochrome P4501B1 (CYP1B1) gene, which is involved in the metabolism of a wide range of environmental toxins and hormones. DESIGN AND METHODS Three hundred (n=300) cases of PTL and equal number of subjects of full term labor (FTL), after excluding all the known risk factors for PTL were included in the study. A two step allele specific PCR was performed for polymorphic analysis of CYP1B1 gene. RESULTS The homozygous variant genotype of CYP1B1*2 (OR=2.97, 95%CI=1.08-8.08, p=0.033) and heterozygous variant of CYP1B1*3 (OR=2.57, 95%CI=1.88-3.63, p=0.001), and CYP1B1*7 (OR=2.59, 95%CI=1.85-3.62, p=0.001) were found to be significantly higher in PTL cases as compared to FTL. CONCLUSIONS The present study demonstrates the possible association of homozygous variant of CYP1B1*2 and heterozygous variant of CYP1B1*3 and CYP1B1*7 genes with the increased risk of PTL.

Polymorphism of glutathione-s-transferase (GSTM1 and T1) in dementia of Alzheimer's type in North Indian population: A preliminary study

University School of Medicine, Suwon, Republic of Korea; Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; MunGyeong Jeil Hospital, Mungyeong-si, Republic of Korea; Konkuk University School of Medicine, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea. Contact e-mail: maumom@gmail.com