title: Metabolic syndrome is linked to chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans.
abstract: The prevalence of metabolic syndrome (MS) has been rising alarmingly worldwide, including in the United States, but knowledge on specific genetic determinants of MS is very limited. Therefore, we planned to identify the genetic determinants of MS as defined by National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) criteria. We performed linkage screen for MS using data from 692 Mexican Americans, who participated in the San Antonio Family Diabetes/Gallbladder Study (SAFDGS). We found strong evidence for linkage of MS on chromosome 7q (LOD = 3.6, empirical P = 6.0 × 10(-5)), between markers D7S2212 and D7S821. In addition, six chromosomal regions exhibited potential evidence for linkage (LOD ≥1.2) with MS. Furthermore, we examined 29 single-nucleotide polymorphisms (SNPs) from the fatty acid translocase (FAT or CD36, 18 SNPs) gene and guanine nucleotide binding protein, α transducing 3 (GNAT3, 11 SNPs) gene, located within the 1-LOD support interval region for their association with MS and its related traits. Several SNPs were associated with MS and its related traits. Remarkably, rs11760281 in GNAT3 and rs1194197 near CD36 exhibited the strongest associations with MS (P = 0.0003, relative risk (RR) = 1.6 and P = 0.004, RR = 1.7, respectively) and several other related traits. These two variants explained ~18% of the MS linkage evidence on chromosome 7q21, and together conferred approximately threefold increase in MS risk (RR = 2.7). In conclusion, our linkage and subsequent association studies implicate a region on chromosome 7q21 to influence MS in Mexican Americans.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA. vfarook@txbiomedgenetics.org
authors.forename: Vidya S
authors.initials: VS
authors.lastname: Farook
authors.forename: Sobha
authors.initials: S
authors.lastname: Puppala
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schneider
authors.forename: Sharon P
authors.initials: SP
authors.lastname: Fowler
authors.forename: Geetha
authors.initials: G
authors.lastname: Chittoor
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Rector
authors.initials: R
authors.lastname: Arya
authors.forename: Mary H
authors.initials: MH
authors.lastname: Black
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Jenkinson
authors.forename: Donna M
authors.initials: DM
authors.lastname: Lehman
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
mesh_terms: D000328:Adult; D018955:CD36 Antigens / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015293:Transducin; D014481:United States / Q000453:epidemiology
chemical_list: D018955:CD36 Antigens; C034809:GNAT1 protein, human; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin