Gustation Genetics: Sweet Gustducin!
CHEMICAL SENSES
Authors: Reed, Danielle R.; Margolskee, Robert F.
Abstract
Two recent studies, the second of which is reported herein, provide evidence that genetic variation in the sweet receptor subunit, TAS1R3, and the second messenger, gustducin (GNAT3), affect the ability of people to correctly sort ascending concentrations of sucrose. These findings raise questions about how variation in the TAS1R3 and GNAT3 gene shape the human sweet tooth and its unwelcome consequences, diabetes and obesity.
Metabolic Syndrome Is Linked to Chromosome 7q21 and Associated With Genetic Variants in CD36 and GNAT3 in Mexican Americans
OBESITY
Authors: Farook, Vidya S.; Puppala, Sobha; Schneider, Jennifer; Fowler, Sharon P.; Chittoor, Geetha; Dyer, Thomas D.; Allayee, Hooman; Cole, Shelley A.; Arya, Rector; Black, Mary H.; Curran, Joanne E.; Almasy, Laura; Buchanan, Thomas A.; Jenkinson, Christopher P.; Lehman, Donna M.; Watanabe, Richard M.; Blangero, John; Duggirala, Ravindranath
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 x 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, alpha 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 similar to 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.
COA
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