TY - JOUR
T1 - Role of the β3-adrenergic receptor locus in obesity and noninsulin- dependent diabetes among members of Caucasian families with a diabetic sibling pair
AU - Elbein, Steven C.
AU - Hoffman, Michael
AU - Barrett, Kelli
AU - Wegner, Kim
AU - Miles, Cindy
AU - Bachman, Kurt
AU - Berkowitz, Dan
AU - Shuldiner, Alan R.
AU - Leppert, Mark F.
AU - Hasstedt, Sandra
PY - 1996
Y1 - 1996
N2 - Obesity and insulin resistance are important risk factors for the development of noninsulin-dependent diabetes (NIDDM) and are prevalent among predisposed first degree relatives of diabetic individuals. Recent molecular screening and analysis of a common missense mutation of the β3-adrenergic receptor gene suggested this locus as a strong candidate for increased obesity, earlier age of diabetes onset, and insulin resistance. To test the hypothesis that the β3-adrenergic receptor locus affects diabetes susceptibility, obesity as measured by body mass index, and components of the insulin resistance syndrome, we examined the role of this region in families ascertained for two or more NIDDM siblings. Linkage analysis was conducted using both parametric and nonparametric analyses, including multipoint sibling pair analysis. We found no evidence for linkage to NIDDM as a dichotomous trait and no evidence for linkage to body mass index, waist/hip ratio, insulin levels, or glucose levels as quantitative traits or to reported age of onset among NIDDM individuals. The Trp64Arg missense mutation was present in 11% of the population. The mutation was not associated with NIDDM, and Arg64 carriers did not have earlier NIDDM onset, higher body mass index, or higher waist/hip ratio than Trp64 homozygotes. Among relatives, Arg64 carriers had significantly lower fasting glucose levels and lower waist/hip ratios than Trp64 homozygotes, but no characteristics of the insulin resistance syndrome. We conclude that the β3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.
AB - Obesity and insulin resistance are important risk factors for the development of noninsulin-dependent diabetes (NIDDM) and are prevalent among predisposed first degree relatives of diabetic individuals. Recent molecular screening and analysis of a common missense mutation of the β3-adrenergic receptor gene suggested this locus as a strong candidate for increased obesity, earlier age of diabetes onset, and insulin resistance. To test the hypothesis that the β3-adrenergic receptor locus affects diabetes susceptibility, obesity as measured by body mass index, and components of the insulin resistance syndrome, we examined the role of this region in families ascertained for two or more NIDDM siblings. Linkage analysis was conducted using both parametric and nonparametric analyses, including multipoint sibling pair analysis. We found no evidence for linkage to NIDDM as a dichotomous trait and no evidence for linkage to body mass index, waist/hip ratio, insulin levels, or glucose levels as quantitative traits or to reported age of onset among NIDDM individuals. The Trp64Arg missense mutation was present in 11% of the population. The mutation was not associated with NIDDM, and Arg64 carriers did not have earlier NIDDM onset, higher body mass index, or higher waist/hip ratio than Trp64 homozygotes. Among relatives, Arg64 carriers had significantly lower fasting glucose levels and lower waist/hip ratios than Trp64 homozygotes, but no characteristics of the insulin resistance syndrome. We conclude that the β3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.
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U2 - 10.1210/jc.81.12.4422
DO - 10.1210/jc.81.12.4422
M3 - Article
C2 - 8954053
AN - SCOPUS:10544240360
SN - 0021-972X
VL - 81
SP - 4422
EP - 4427
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -