Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation.

BACKGROUND: Maternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. OBJECTIVES: This study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. METHODS: A diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. RESULTS: We showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%-70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. CONCLUSIONS: Maternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role.

Hypoxia Inducible Factors (HIF1α and HIF3α) are differentially methylated in preeclampsia placentae and are associated with birth outcomes.

Preeclampsia is a placental vascular pathology and hypoxia is known to influence placental angiogenesis. Hypoxia Inducible Factors (HIF1α and HIF3α) mediate the response to cellular oxygen concentration and bind to hypoxia response element of target genes. However the mechanism regulating above activity is not well-understood. We investigated if placental DNA methylation (DNAm) and expression of HIF1α and 3α genes are altered and associated with pre-eclampsia, placental weight and birth outcomes. Using a cohort comprising women with preeclampsia [N = 100, delivering at term (N = 43) and preterm (N = 57)] and normotensive controls (N = 100), we analysed DNAm in HIF1α and 3α, and their mRNA expression in placentae, employing pyrosequencing and quantitative real-time PCR, respectively. We observed significant hypermethylation at cg22891070 of HIF3α in preeclampsia placentae compared to controls (ß = 1.5%, p = 0.04). CpG8 in the promoter region of HIF1α, showed marginally significant hypomethylation in preterm preeclampsia compared to controls (ß = - 0.15%, p = 0.055). HIF1α expression was significantly lower in preterm preeclampsia compared to controls (mean ± SE = 10.16 ± 2.00 vs 4.25 ± 0.90, p = 0.04). Further, DNAm in HIF1α promoter region was negatively associated with its expression levels (ß = - 0.165, p = 0.024). Several CpGs in HIF1α were negatively associated with placental weight and birth outcomes including birth weight (ß range = - 0.224-0.300) and birth length [ß range = - 0.248 to - 0.301 (p < 0.05 for all)]. Overall, we demonstrate altered DNAm in HIF1α and HIF3α in preeclampsia placentae, also associated with various birth outcomes. Correlation of DNAm in HIF1α and its expression suggests a possible role in the pathogenesis of pre-eclampsia. Further investigations on interactions between HIF1α and HIF3α in preeclampsia would be interesting.

MTR, MTRR and CBS Gene Polymorphisms in Recurrent Miscarriages: A Case Control Study from North India.

Background: According to various epidemiological studies, the aetiology of recurrent miscarriages (RMs) is multifactorial. The goal of this study is to learn more about the link between genetic polymorphisms and RM. Aim: To evaluate the association of 5-Methytetrahydrofolate-Homocysteine Methyltransferase (MTR) A2756G, 5-Methytetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) A66G and cystathionine beta-synthase (CBS) 844INS68 genetic polymorphisms with RM and also to understand the combined effect of the selected genotypes. Study Setting and Design: This was a hospital-based, case-control, observational study. Materials and Methods: A total of 516 participants were recruited in the present study, of which 200 RM cases and 258 controls were included in the present study. Fasting blood sample (~5ml) was drawn from all the participants and were screened for genetic polymorphisms of MTR A2756G, MTRR A66G and CBS 844INS68. Statistical Analysis: The frequency, odd's ratio and Hardy-Weinberg equilibrium were evaluated. SPSS (version 21.0) was used for the data analysis. Results: MTR A2756G genetic polymorphism was not associated with the risk of RM. The ancestral allele of MTRR A66G and the mutant allele of CBS 844INS68 was causing an increased risk of more than two folds for RM. CBS 844INS68 in combination with MTR A2756G was found to pose an increased risk of more than two folds for RM. Conclusion: Genetic polymorphisms particularly MTRR A66G and CBS 844INS68 seems to be elevating the risk and hence making women susceptible for RM.

Association of placental fatty acid desaturase 2 (FADS2) methylation with maternal fatty acid levels in women with preeclampsia.

INTRODUCTION: Biosynthesis of long-chain polyunsaturated fatty acids requires sequential activities of desaturases and elongases for conversion of fatty acid precursors to products. The delta-6 desaturase enzyme, encoded by FADS2 gene, is a rate limiting enzyme in this pathway. Alterations in D6D enzyme activity can lead to altered fatty acid profiles. OBJECTIVES: To examine differences in placental DNA methylation (DNAm) and expression of FADS2 gene in preeclampsia women compared to normal women and their association with maternal variables (plasma fatty acids, desaturase enzyme index, blood pressure), placental weight and birth outcomes. METHODS: DNAm and expression of FADS2 gene were examined in placentae of normotensive (n = 100) control and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Women with preeclampsia included those delivering at term (n = 43, gestation ≥ 37 weeks; T-PE) or preterm (n = 57, gestation < 37 weeks; PT-PE). A total of 26 CpGs in FADS2 promoter and region around it, were analysed in two PCR reactions (region 1 and 2). RESULTS: Out of 13 CpGs in region 1, significant hypermethylation was noted at CpG3 in T-PE (p = 0.03) and of 13 CpGs in region 2, CpG2 (p = 0.008), CpG11 (p = 0.04), CpG12 (p = 0.001) were hypomethylated and CpG13 (p = 0.001) was hypermethylated in preeclampsia group, as compared to controls. FADS2 expression was lower in PT-PE as compared to controls (p = 0.04). DNAm at various CpGs in the FADS2 were associated with maternal plasma FADS2 enzyme index and also associated with maternal fatty acid levels. However, we did not observe any association of DNAm with maternal blood pressure, placental weight and birth outcomes. CONCLUSIONS: This study for the first time reports differential methylation of FADS2 and its association with impaired maternal fatty acid metabolism in preeclampsia and provides a mechanistic basis to our earlier observations of altered maternal LCPUFA levels in women with preeclampsia.

Maternal one carbon metabolism and interleukin-10 &-17 synergistically influence the mode of delivery in women with Early Onset Pre-Eclampsia.

OBJECTIVE: Studies on One Carbon Metabolism (OCM), Interleukins-10 &-17 (IL-10/-17) & ßhCG in pre-eclampsia and its delivery outcome (preterm birth) reveal contradictory results, attributed to clinical heterogeneity (early/late onset pre-eclampsia) or preterm/term birth. Disturbed OCM also influences IL-10 &-17 during pregnancy. We sought to investigate the synergism between OCM and IL-10/-17 mediated immune-regulation through ßhCG in Early onset pre-eclampsia (EO-PE) patients, delivering preterm, among North Indian women. STUDY DESIGN: Case-control study with a total of 399 pregnant women (EO-PE delivering preterm = 199; Normotensives delivering at term = 200). Maternal genotypes & biochemical estimations along with fetal genotypes on subset (n = 72) pertaining to OCM and IL-10/-17 regulation were assessed. MAIN OUTCOME MEASURES: Association of 1) maternal plasma levels with EO-PE 2) maternal and fetal genotypes with EO-PE. 3) Effect of Hyper-homocysteinemia (surrogate of disturbed OCM) on differential immune regulation (IL10,-17, ßhCG) in EO-PE and mode of delivery. RESULTS: Hyper-homocysteinemia posed an increased risk of three folds for EO-PE. Both, folate and B12 deficiencies were associated with elevated homocysteine in EO-PE. Further, MTHFR 677TT homozygotes was present only in EO-PE indicating its detrimental role. However, maternal IL17-197AA genotype showed decreased risk for EO-PE. Furthermore, elevated maternal plasma IL-17 along with elevated IL-10 & ßhCG were observed in EO-PE. Taken together, altered homocysteine metabolism was associated with high IL10 in EO-PE; and was more pronounced in spontaneous vaginal deliveries as compared to induced/caesarean section deliveries. CONCLUSIONS: We report homocysteine mediated IL-10 &17 dysregulation and its influence on mode of delivery in EO-PE, possibly through initiation of cervical ripening. Further, these could serve potential biomarkers of EO-PE & its delivery outcome among vulnerable populations with similar nutritional & genetic predispositions.

Placental growth factor and Fms related tyrosine kinase-1 are hypomethylated in preeclampsia placentae.

Aim: This study aims to examine the DNA methylation (DNAm) and expression patterns of genes associated with placental angiogenesis in preeclampsia. Materials & methods: DNAm and expression were examined in normotensive (n = 100) and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Results: Hypomethylation at several CpGs was observed in PlGF and FLT-1 in women with preeclampsia compared to normotensive controls. PlGF expression was lower in women with preeclampsia while FLT-1 expression was comparable. DNAm at various CpGs was negatively correlated with expression in both the genes and were associated with maternal blood pressure and birth outcomes. Conclusion: DNAm and expression of angiogenic factors in placentae are differentially regulated in preeclampsia and influence birth outcomes.

Maternal vitamin B12 deficiency in rats alters DNA methylation in metabolically important genes in their offspring.

Vitamin B12 deficiency is a critical problem worldwide and peri-conceptional deficiency of this vitamin is associated with the risk of complex cardio-metabolic diseases. Nutritional perturbations during these stages of development may lead to changes in the fetal epigenome. Using Wistar rat model system, we have earlier shown that low maternal B12 levels are associated with low birth weight, adiposity, insulin resistance, and increased triglyceride levels in the offspring, which might predispose them to the risk of cardio-metabolic diseases in adulthood. In this study, we have investigated the effects of maternal B12 deficiency on genome-wide DNA methylation profile of the offspring and the effect of rehabilitation of mothers with B12 at conception. We have performed methylated DNA immunoprecipitation sequencing of liver from pups in four groups of Wistar rats: Control (C), B12-restricted (B12R), B12-rehabilitated at conception (B12RC), and B12-rehabilitated at parturition (B12RP). We have analyzed differentially methylated signatures between the three groups as compared to controls. We have identified a total of 214 hypermethylated and 142 hypomethylated regions in the 10 kb upstream region of transcription start site in pups of B12-deficient mothers, which are enriched in genes involved in fatty acid metabolism and mitochondrial transport/metabolism. B12 rehabilitation at conception and parturition is responsible for reversal of methylation status of many of these regions to control levels suggesting a causal association with metabolic phenotypes. Thus, maternal B12 restriction alters DNA methylation of genes involved in important metabolic processes and influences the offspring phenotype, which is reversed by B12 rehabilitation of mothers at conception.

Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India.

AIM: The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism. METHODS: The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP. RESULTS HIGHER: Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts. CONCLUSION: The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.

Impaired Homocysteine Metabolism Associated with High Plasma Interleukin-17A Levels, a Pro-Atherogenic Marker, in an Endogamous Population of North India.

Background: Impaired homocysteine metabolism (IHM; hyperhomocysteinemia) has been linked with many complex disorders like cardiovascular diseases and immunological disturbances. However, studies understanding IHM in light of pro- and anti- atherogeneic markers like Interleukin-17A & -10 (IL-17A & IL-10) and Forkhead box p3 (Foxp3, a master transcription factor) are scarce. Aim: In our present study, we aimed to understand the relation of IHM with plasma IL-17A and IL-10 levels and Foxp3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from an endogamous population (Jats of Haryana, North India) with high prevalence of IHM without the concurrence of significant adverse cardiovascular outcomes. Methods: Forty (40) clinically healthy individuals, unrelated up to first cousins, were recruited and were subjected to demographic, physiological and anthropometric profiling, followed by intravenous blood sample collection (fasting) and lipid profiling. Plasma homocysteine levels were estimated and individuals with homocysteine levels ≥ 15umol/L and <15umol/L were categorized as the impaired homocysteine metabolism group (IHM, n=30) and normal homocysteine metabolism group (NHM, n=10) respectively. Plasma folate and vitamin B12 and MTHFR C677T (methylenetetrahydrofolate reductase) polymorphism were detected. Relative mRNA expression of Foxp3 in PBMCs (normalized to 18S) was quantitated using SyBR green technology. Plasma IL-10 & 17 levels were estimated by ELISA assays. Results and Conclusions: None of the physiological, anthropometric and lipid variables were different between the two groups. Foxp3 mRNA expression levels were relatively lower, and plasma IL-10 levels were found to be comparable among IHM and NHM group. However, significantly higher IL-17A levels and relatively high LDL cholesterol levels were present in the IHM group as compared with NHM. Our findings suggest that the Jats of Haryana, North India, exhibiting high levels of homocysteine, might also carry the high IL-17A -pro-atherogenic marker, suggesting an increasing burden of pre-morbid condition. This apparently does not reach to significant mortality/morbidity attributed to the counter action or balancing act of IL-10 (an anti-atherogenic marker). This further suggests environment-influenced epigenetic control mechanisms of the targeted genes in the present population.

Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism.

Background: Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course. Methods: We review human intergenerational studies using a three-part search strategy. Search 1 investigates associations between preconceptional or pregnancy nutritional exposures, focusing on one-carbon metabolism, and offspring DNA methylation. Search 2 considers associations between offspring DNA methylation at genes found in the first search and growth-related, cardiometabolic and cognitive outcomes. Search 3 isolates those studies explicitly linking maternal nutritional exposure to offspring phenotype via DNA methylation. Finally, we compile all candidate genes and regions of interest identified in the searches and describe their genomic locations, annotations and coverage on the Illumina Infinium Methylation beadchip arrays. Results: We summarize findings from the 34 studies found in the first search, the 31 studies found in the second search and the eight studies found in the third search. We provide details of all regions of interest within 45 genes captured by this review. Conclusions: Many studies have investigated imprinted genes as priority loci, but with the adoption of microarray-based platforms other candidate genes and gene classes are now emerging. Despite a wealth of information, the current literature is characterized by heterogeneous exposures and outcomes, and mostly comprise observational associations that are frequently underpowered. The synthesis of current knowledge provided by this review identifies research needs on the pathway to developing possible early life interventions to optimize lifelong health.

Methylenetetrahydrofolate Reductase Gene-specific Methylation and Recurrent Miscarriages: A Case- Control Study from North India.

AIM: This study aimed to understand the association of gene-specific methylation of the promoter region of methylenetetrahydrofolate reductase (MTHFR) in the causation of recurrent miscarriages (RMs) both independently and also in light of MTHFR C677T polymorphism, hyperhomocysteinemia, folate, and Vitamin B12 deficiency. SETTINGS AND DESIGN: This was a hospital-based, case-control, observational study. METHODS: The proposed study included a total of 85 RM cases and 121 nonpregnant controls. Biochemical (homocysteine, folate, and Vitamin B12) investigations, MTHFR polymorphism (C677T), and MTHFR allele-specific methylation were done on all the samples. RESULTS: Methylation-specific polymerase chain reaction of MTHFR gene revealed that methylated allele (single dose) was found to pose a significant 3.6-fold increased risk for RM. The degree of risk of methylated allele for RM was found to be aggravated from the normal genotype CC (2.8 folds) to CT (7.5 folds) individuals. Vitamin B12 deficiency and folate repletion were found to be posing an increased risk in association with methylated allele for recurrent miscarriages as compared to the respective controls. CONCLUSION: Recurrent miscarriage cases were found to be hypermethylated with respect to MTHFR gene-specific methylation as compared to the controls. High prevalence of folate repletion causing imbalance between folate and Vitamin 12 levels may lead to hypermethylation among recurrent miscarriage cases. The present study highlights the significance of the epigenetic mechanisms in the causation of the recurrent miscarriages.

Hypermethylated CpG sites in the MTR gene promoter in preterm placenta.

AIM: Altered maternal one-carbon metabolism influences placental DNA methylation patterns and 'programs' the fetus for noncommunicable diseases in adult life. EXPERIMENTAL PROCEDURES: Levels of plasma folate, vitamin B12, homocysteine, mRNA and protein levels of MTHFR and MTR enzymes in placenta were compared among women delivering preterm (n = 83) and term (n = 75). MTR promoter CpG methylation was undertaken. RESULTS: MTHFR and MTR mRNA levels were higher while protein levels were lower, and MTR CpG sites were hypermethylated in the preterm group, as compared with the term group. Methylated CpG sites were negatively associated with maternal plasma vitamin B12 levels. CONCLUSION: Study suggests a dysregulation of enzyme genes in remethylation arm of the one-carbon metabolism in placenta of women delivering preterm.

MTHFR C677T polymorphism, folate, vitamin B12 and homocysteine in recurrent pregnancy losses: a case control study among North Indian women.

AIM: The present study attempts to understand the role of methylenetetrahydrofolate reductase C677T (MTHFR C677T) in recurrent pregnancy losses in North Indian women because of hyperhomocysteinemia in light of serum folate and vitamin B12. METHODS: One hundred and seven women with three or more consecutive unexplained recurrent pregnancy losses and 343 women with two or more successful and uncomplicated pregnancies were recruited. Plasma homocysteine, serum folate and vitamin B12 were analyzed using chemiluminescence. MTHFR C677T detection was completed in all subjects. RESULTS: MTHFR genotypic distribution among cases and controls showed no significant difference (P=0.409). However, MTHFR C677T polymorphism was found to be significantly associated with increased homocysteine in the case group (P=0.031). Hyperhomocysteinemia and vitamin B12 deficiency were found to be significant risk factors for recurrent pregnancy loss (RPL) (OR=7.02 and 16.39, respectively). Folate deficiency was more common in controls (63.47%) as compared to the case group (2.56%). CONCLUSION: Low vitamin B12 increases homocysteine, specifically among T allele carrying case mothers, suggesting T allele is detrimental with B12 deficiency. The study emphasizes the importance of vitamin B12 in the prevention of RPL in North Indian women.

Genetic thromobophilia in pregnancy: a case-control study among North Indian women.

In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa.

The association of non-HDL cholesterol with the presence of metabolic syndrome in North Indian subjects with and without CAD.

AIM: The present study aims to identify which lipid parameter is significantly associated with Coronary Artery Disease (CAD) and metabolic syndrome (MetS) and also to find out the association of non-HDL cholesterol (non-HDL-C) with the presence of MetS in North Indian subjects with and without CAD. SUBJECTS AND METHODS: One hundred and thirteen CAD and 140 non-CAD (controls) aged 35-75 years were recruited for the study, matched for ethnicity and geography after obtaining their written informed consent. The CAD patients were identified based on their medical diagnostic history. Height, weight, waist and hip circumferences, blood pressures (systolic and diastolic) and lipid profile were measured for all the subjects. RESULTS: Sixty-nine out of 113 (61.06%) of CAD and 52/140 (37.1%) of non-CAD had MetS. Age standardized prevalence of MetS was 23.2% and 16.1% in CAD and non-CAD individuals, respectively. Age standardized prevalence of metabolic abnormalities in the CAD group was in the order of abdominal obesity>non-HDL-C>systolic blood pressure (SBP) > triglyceride (TG) > total cholesterol (TC) > diastolic blood pressure (DBP) > Low Density Lipoprotein Cholesterol (LDL-C) > High Density Lipoprotein Cholesterol (HDL-C). Non-HDL-C, TG and HDL-C were found to be significantly associated with MetS. CONCLUSIONS: TG and HDL-C are established risk components included in the characterization of MetS; but significant association of non-HDL-C with MetS in the present study is a key finding. The study focuses on the use of non-HDL-C as a simple screening tool to identify individuals with clustering metabolic abnormalities which increase the propensity for CAD.