TY - JOUR
T1 - TRP64ARG β3-adrenergic receptor and obesity in Mexican Americans
AU - Silver, Kristi
AU - Mitchell, Braxton D.
AU - Walston, Jeremy
AU - Sorkin, John D.
AU - Stern, Michael P.
AU - Roth, Jesse
AU - Shuldiner, Alan R.
N1 - Funding Information:
Acknowledgements We thank Keith Tanner for technical assistance. This work was supported by a Paul Beeson Faculty Scholar Award from the American Federation of Aging Research (A.R.S.), Brookdale National Fellowship (J.W.), the Chesapeake Education and Research Trust (J.W., K.S., A.R.S.), and the National Institutes of Health, National Research Service award 1F32DK09340-01 (K.S.) and National Institutes of Health grants RO1DK49692-03 (A.R.S.), 5T32AG00120, and R01DK42273.
PY - 1997
Y1 - 1997
N2 - The β3-adrenergic receptor (β3AR) is expressed in visceral fat and is a regulator of resting metabolic rate, thermogenesis, and lipolysis. We genotyped 61 unrelated Mexican Americans for a variant in the β3AR gene (codon 64 TGG(Trp)→CGG(Arg); TRP64ARG). The allele frequency was 0.13. The TRP64ARG variant was significantly associated with an earlier age of onset of noninsulin-dependent diabetes mellitus (41.3 ± 4.6 years vs 55.6 ± 2.6 years; P < 0.02) and in non-diabetics, with elevated 2-h insulin levels during an oral glucose tolerance test (810 ± 120 pmol/l vs 384 ± 6 pmol/l; P < 0.005). Nondiabetic subjects with the variant allele tended to have higher body mass indices (BMI), waist-to-hip ratios, and diastolic blood pressures. The study group was expanded to include 421 related subjects from 31 families in the San Antonio Family Diabetes Study. Using a measured genotype analysis approach to estimate genotype-specific means for each trait, those who were homozygous for the TRP64ARG variant had significantly higher 2-h insulin levels (P = 0.036) and trends towards higher BMI compared to the other two genotypes. We detected no associations of these traits in the TRP64ARG heterozygotes in the larger group. We conclude that the TRP64ARG β3AR variant is a susceptibility gene for several features of the insulin resistance syndrome in Mexican Americans. Since its effects are modest, study design (e.g., subject selection, genetic background, and statistical analyses) may influence which traits are associated with this variant and whether or not the effect is detectable in heterozygotes.
AB - The β3-adrenergic receptor (β3AR) is expressed in visceral fat and is a regulator of resting metabolic rate, thermogenesis, and lipolysis. We genotyped 61 unrelated Mexican Americans for a variant in the β3AR gene (codon 64 TGG(Trp)→CGG(Arg); TRP64ARG). The allele frequency was 0.13. The TRP64ARG variant was significantly associated with an earlier age of onset of noninsulin-dependent diabetes mellitus (41.3 ± 4.6 years vs 55.6 ± 2.6 years; P < 0.02) and in non-diabetics, with elevated 2-h insulin levels during an oral glucose tolerance test (810 ± 120 pmol/l vs 384 ± 6 pmol/l; P < 0.005). Nondiabetic subjects with the variant allele tended to have higher body mass indices (BMI), waist-to-hip ratios, and diastolic blood pressures. The study group was expanded to include 421 related subjects from 31 families in the San Antonio Family Diabetes Study. Using a measured genotype analysis approach to estimate genotype-specific means for each trait, those who were homozygous for the TRP64ARG variant had significantly higher 2-h insulin levels (P = 0.036) and trends towards higher BMI compared to the other two genotypes. We detected no associations of these traits in the TRP64ARG heterozygotes in the larger group. We conclude that the TRP64ARG β3AR variant is a susceptibility gene for several features of the insulin resistance syndrome in Mexican Americans. Since its effects are modest, study design (e.g., subject selection, genetic background, and statistical analyses) may influence which traits are associated with this variant and whether or not the effect is detectable in heterozygotes.
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U2 - 10.1007/s004390050633
DO - 10.1007/s004390050633
M3 - Article
C2 - 9439659
AN - SCOPUS:0031432923
SN - 0340-6717
VL - 101
SP - 306
EP - 311
JO - Human genetics
JF - Human genetics
IS - 3
ER -