title: Genetic variant of AMD1 is associated with obesity in urban Indian children.
abstract: BACKGROUND
  Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.
  
  
  RESULTS
  We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10(-4)] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10(-3)] and meta-analysis [OR = 1.35, P = 1.9×10(-6)]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.
  
  
  CONCLUSIONS
  Our study provides first evidence for the association of AMD1 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.
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rubina
authors.initials: R
authors.lastname: Tabassum
authors.forename: Alok
authors.initials: A
authors.lastname: Jaiswal
authors.forename: Ganesh
authors.initials: G
authors.lastname: Chauhan
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Dwivedi
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Raman K
authors.initials: RK
authors.lastname: Marwaha
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000235:genetics*; D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007194:India / Q000453:epidemiology; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction; D014505:Urban Population
chemical_list: D020738:Leptin; D006710:Homocysteine; D004247:DNA; D012437:Adenosylmethionine Decarboxylase