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Common variants in the beta2-(Gln27Glu) and beta3-(Trp64Arg)--adrenoceptor genes are associated with elevated serum NEFA concentrations and type II diabetes

Carlsson, M; Orho-Melander, Marju LU ; Hedenbro, J and Groop, Leif LU (2001) In Diabetologia 44(5). p.629-636
Abstract
AIMS/HYPOTHESIS: Higher NEFA concentrations predict Type II (non-insulin-dependent) diabetes mellitus but it is not known whether higher NEFA concentrations are genetically determined or reflect coexisting obesity. To address this question we studied whether common variants in two genes encoding for key regulators of lipolysis, the beta2- and beta3- adrenoceptors (B2AR and B3AR) are associated with NEFA concentrations and Type II diabetes. METHODS: A total of 1054 Swedish subjects with varying degrees of glucose tolerance were genotyped for the Gln27Glu variant in the B2AR and for the Trp64Arg variant in the B3AR genes using PCR-RFLP. RESULTS: The B2AR Gln27 allele was more frequent in 219 Type II diabetic patients than in 237 non-diabetic... (More)
AIMS/HYPOTHESIS: Higher NEFA concentrations predict Type II (non-insulin-dependent) diabetes mellitus but it is not known whether higher NEFA concentrations are genetically determined or reflect coexisting obesity. To address this question we studied whether common variants in two genes encoding for key regulators of lipolysis, the beta2- and beta3- adrenoceptors (B2AR and B3AR) are associated with NEFA concentrations and Type II diabetes. METHODS: A total of 1054 Swedish subjects with varying degrees of glucose tolerance were genotyped for the Gln27Glu variant in the B2AR and for the Trp64Arg variant in the B3AR genes using PCR-RFLP. RESULTS: The B2AR Gln27 allele was more frequent in 219 Type II diabetic patients than in 237 non-diabetic subjects (59.8 % vs 52.3 %; OR = 1.72, p = 0.02) while there was no significant difference in the frequency of the B3AR Arg64 allele. Subjects homozygous for the protective alleles (Glu27 and Trp64) had, however, a lower prevalence of diabetes than subjects with other genotype combinations (OR = 0.58, p = 0.03). Among sibling pairs discordant for the B2AR Gln27Glu polymorphism, siblings with an excess of the Gln27 allele had higher fasting insulin (n = 217; p = 0.02) and NEFA concentrations (107 sex-matched pairs; p = 0.01) than siblings with an excess of the Glu27 allele. Among sibling pairs discordant for the B3AR Trp64Arg variant, siblings with the Arg64 allele had higher 2 h glucose (n = 48; p = 0.01) and NEFA concentrations (16 pairs matched for sex; p < 0.04) than siblings with the Trp64Trp64 genotype. CONCLUSIONS/INTERPRETATION: Common variants in the beta2- and beta3- adrenoceptor genes are associated with increased fasting insulin and NEFA concentrations and could increase susceptibility to Type II diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
β2-adrenoreceptor, β3-adrenoreceptor, insulin, lipolysis, Type II diabetes, Non-esterified fatty acids
in
Diabetologia
volume
44
issue
5
pages
629 - 636
publisher
Springer Verlag
external identifiers
  • pmid:11380082
  • scopus:0034744185
ISSN
1432-0428
DOI
10.1007/s001250051670
language
English
LU publication?
yes
id
9dc28866-ec81-4a2d-abf9-d78343485c23 (old id 1122551)
date added to LUP
2008-06-25 15:49:02
date last changed
2018-01-07 05:22:15
@article{9dc28866-ec81-4a2d-abf9-d78343485c23,
  abstract     = {AIMS/HYPOTHESIS: Higher NEFA concentrations predict Type II (non-insulin-dependent) diabetes mellitus but it is not known whether higher NEFA concentrations are genetically determined or reflect coexisting obesity. To address this question we studied whether common variants in two genes encoding for key regulators of lipolysis, the beta2- and beta3- adrenoceptors (B2AR and B3AR) are associated with NEFA concentrations and Type II diabetes. METHODS: A total of 1054 Swedish subjects with varying degrees of glucose tolerance were genotyped for the Gln27Glu variant in the B2AR and for the Trp64Arg variant in the B3AR genes using PCR-RFLP. RESULTS: The B2AR Gln27 allele was more frequent in 219 Type II diabetic patients than in 237 non-diabetic subjects (59.8 % vs 52.3 %; OR = 1.72, p = 0.02) while there was no significant difference in the frequency of the B3AR Arg64 allele. Subjects homozygous for the protective alleles (Glu27 and Trp64) had, however, a lower prevalence of diabetes than subjects with other genotype combinations (OR = 0.58, p = 0.03). Among sibling pairs discordant for the B2AR Gln27Glu polymorphism, siblings with an excess of the Gln27 allele had higher fasting insulin (n = 217; p = 0.02) and NEFA concentrations (107 sex-matched pairs; p = 0.01) than siblings with an excess of the Glu27 allele. Among sibling pairs discordant for the B3AR Trp64Arg variant, siblings with the Arg64 allele had higher 2 h glucose (n = 48; p = 0.01) and NEFA concentrations (16 pairs matched for sex; p &lt; 0.04) than siblings with the Trp64Trp64 genotype. CONCLUSIONS/INTERPRETATION: Common variants in the beta2- and beta3- adrenoceptor genes are associated with increased fasting insulin and NEFA concentrations and could increase susceptibility to Type II diabetes.},
  author       = {Carlsson, M and Orho-Melander, Marju and Hedenbro, J and Groop, Leif},
  issn         = {1432-0428},
  keyword      = {β2-adrenoreceptor,β3-adrenoreceptor,insulin,lipolysis,Type II diabetes,Non-esterified fatty acids},
  language     = {eng},
  number       = {5},
  pages        = {629--636},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Common variants in the beta2-(Gln27Glu) and beta3-(Trp64Arg)--adrenoceptor genes are associated with elevated serum NEFA concentrations and type II diabetes},
  url          = {http://dx.doi.org/10.1007/s001250051670},
  volume       = {44},
  year         = {2001},
}