Background Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases,

Background Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis. Conclusions/Significance Our study provides first evidence for the association of variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken. Introduction Childhood obesity is a growing public health issue worldwide [1]. Prevalence of obese/weight problems has improved from 16% in 2002 to 24% in 2006 in metropolitan school kids in Delhi, India [2]. Both environmental and hereditary factors play a significant role in the introduction of obesity. Studies looking into the genetic element of weight problems have primarily centered on adult weight problems and around 32 weight problems susceptibility genes have already been identified through huge size genome wide association research (GWAS) [3]. The seek out genetic risk elements for years as a child weight problems and related phenotypes are primarily limited by the replication of variations determined through genome wide association research (GWAS) in adults [3]. Years as a child weight problems is among the major determinants of many chronic diseases in adulthood such as type 2 diabetes, hypertension and cardio-vascular diseases [4]. Manifestation of these chronic metabolic disorders, which have become pandemic in India [5]C[7], starts in 446-86-6 IC50 early life [8]. Indian subjects with impaired glucose tolerance or diabetes are shown to have typically low BMI up to the age of two years, followed by increasing BMI at the age of 12 years [8]. This suggests that molecular events leading to obesity in childhood predispose individuals to chronic metabolic disorders in later life. This makes identification of factors linking childhood obesity and adult chronic disorders 446-86-6 IC50 very imperative. Elevated level of homocysteine, termed as hyperhomocysteinemia, is regarded as a potential risk factor for cardiovascular diseases, diabetes, hypertension and number of other pathologies [9]C[12]. Homocysteine is usually a thiol made up of 446-86-6 IC50 amino acid which plays an important role in cell metabolism. The metabolic traffic of homocysteine occurs either via remethylation to methionine or through irreversible trans-sulfuration to cysteine. Homocysteine metabolism involves 446-86-6 IC50 a series of enzymatic reactions that produce variety of metabolic intermediates which are important for cellular processes such as transmethylation, transulfuration and polyamine biosynthesis (Physique 1) Rabbit Polyclonal to Galectin 3 [13]. Perturbations in the activities of enzymes involved in these processes such as methylene tetrahydrofolate reductase (MTHFR), methylene tetrahydrofolate dehydrogenase (MTHFD), methionine synthase reductase (MTRR), cystathionine bsynthase (CBS) may results in altered levels of homocysteine and thus metabolic disorders. Physique 1 Homocysteine metabolism pathway. Contribution of variants in homocysteine pathway genes to susceptibility of diabetes, obesity and vascular diseases 446-86-6 IC50 has been suggested by previous studies [14]C[16]. Genetic variants of and have been shown to be associated with obesity [17]. The C677T polymorphism of is usually reported to be associated with hyperhomocysteinemia, type 2 diabetes and related complications [18], [19]. However there is no report of association of homocysteine pathway genes with childhood obesity. Here we hypothesized that genetic variant in homocysteine metabolism pathway genes leading to perturbation in homocysteine metabolism might be a link between childhood obesity and adult metabolic disorders. To test this, we designed the present two stage case-control study to investigate association of 90 common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children. Materials and Methods Ethics Statement The study was carried out in accordance with the principles of Helsinki Declaration and was approved by Human Ethics Committee of Institute of Genomics and Integrative Biology (CSIR) and All India Institute of Medical Sciences Research Ethics Committee. Informed written consent was.

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