PMID- 10404816
OWN - NLM
STAT- MEDLINE
DCOM- 19990726
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 7
DP  - 1999 Jul
TI  - Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor 
      that is associated with reduced basal metabolic rate in obese subjects.
PG  - 2429-33
AB  - The alpha2-adrenergic receptors mediate part of the actions of the catecholamines
      noradrenaline and adrenaline on the regulation of energy balance. As part of an
      ongoing study on the genetics of obesity, the entire coding sequence of the
      alpha2B-adrenoceptor gene was screened in 58 obese, nondiabetic Finns by
      PCR-single stranded conformational analysis (PCR-SSCA). A polymorphism that leads
      to a deletion of 3 glutamic acids from a glutamic acid repeat element (Glu x 12, 
      amino acids 297-309) present in the third intracellular loop of the receptor
      protein was identified. This repeat element has previously been shown to be
      important for agonist-dependent receptor desensitization. Of 166 genotyped
      subjects, 47 (28%) had 2 normal (long) alleles (Glu12/Glu12), 90 (54%) were
      heterozygous (Glu12/Glu9), and 29 (17%) were homozygous for the short (Glu9/Glu9)
      form. The basal metabolic rate, determined by indirect calorimetry and adjusted
      for fat-free body mass, fat mass, sex, and age, was 94 Cal/day (5.6%) lower (95% 
      confidence interval for difference, 32, 156) in subjects homozygous for the short
      allele than in subjects with two long alleles (F = 4.84; P = 0.009, by ANOVA).
      Thus, a genetic polymorphism of the alpha2B-adrenoceptor subtype can partly
      explain the variation in basal metabolic rate in an obese population and may
      therefore contribute to the pathogenesis of obesity.
FAU - Heinonen, P
AU  - Heinonen P
AD  - Department of Pharmacology and Clinical Pharmacology, University of Turku,
      Finland.
FAU - Koulu, M
AU  - Koulu M
FAU - Pesonen, U
AU  - Pesonen U
FAU - Karvonen, M K
AU  - Karvonen MK
FAU - Rissanen, A
AU  - Rissanen A
FAU - Laakso, M
AU  - Laakso M
FAU - Valve, R
AU  - Valve R
FAU - Uusitupa, M
AU  - Uusitupa M
FAU - Scheinin, M
AU  - Scheinin M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - AIM
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Basal Metabolism/*genetics
MH  - Calorimetry, Indirect
MH  - Female
MH  - Glutamic Acid/genetics
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Obesity/*genetics/metabolism
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Receptors, Adrenergic, alpha/*chemistry/genetics
MH  - Repetitive Sequences, Amino Acid
MH  - *Sequence Deletion
EDAT- 1999/07/15 00:00
MHDA- 1999/07/15 00:01
CRDT- 1999/07/15 00:00
PHST- 1999/07/15 00:00 [pubmed]
PHST- 1999/07/15 00:01 [medline]
PHST- 1999/07/15 00:00 [entrez]
AID - 10.1210/jcem.84.7.5818 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Jul;84(7):2429-33. doi: 10.1210/jcem.84.7.5818.