Exp Clin Endocrinol Diabetes 2001; 109(8): 402-405
DOI: 10.1055/s-2001-18993
Articles

© Johann Ambrosius Barth

No evidence for involvement of alleles of the 825-C/T polymorphism of the G-protein subunit β3 in body weight regulation

A. Hinney 1 , F. Geller 2 , T. Neupert 1 , C. Sommerlad 1 , G. Gerber 1 , T. Görg 2 , W. Siegfried 3 , H. Goldschmidt 4 , H. Remschmidt 1 , A. Ziegler 2 , J. Hebebrand 1
  • 1 Clinical Research Group, Department of Child and Adolescent Psychiatry, Philipps-University of Marburg, Germany
  • 2 Institute of Medical Biometry and Epidemiology, Philipps-University of Marburg, Germany
  • 3 Obesity Treatment Centre Insula, Berchtesgaden, Germany
  • 4 Spessart Klinik, Bad Orb, Germany
Further Information

Publication History

Publication Date:
13 December 2001 (online)

Summary:

The 825-C/T polymorphism of the β3 subunit of the heterotrimeric G protein gene (GNB3) has been shown to be associated with essential hypertension in humans. Recently, it was also reported that the 825-T allele has a higher frequency in obese than non-obese hypertensives suggesting that the primary effect of this allele is on body weight. The association to hypertension might merely be a secondary effect of the higher weight of the respective allele carriers. - To investigate an involvement of the 825-T allele in body weight regulation in young individuals, we evaluated allele frequencies in 440 extremely obese children and adolescents (82.9% had a body mass index [BMI] ≥ 99th percentile), 51 obese students (BMI ≥ 90th percentile), 110 normal weight students (BMI between 40th and 60th percentile) and 144 underweight students (BMI ≤ 15th percentile). The study groups were genotyped by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The one-sided Yates-corrected χ 2-test and the Cochran-Armitage trend test for association were performed. Tests for association were negative. The 825-T allele frequencies were similar in the four study groups belonging to different weight ranges (extreme early onset obesity: 0.29; obesity: 0.28; normal weight: 0.35; underweight: 0.32). Similarly, genotype frequencies did not differ between the groups. We concluded that the 825-T allele of the GNB3 does not play a major role in weight regulation in German children, adolescents and young adults.

References

  • 1 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. American Psychiatric Association, Washington 539-550 1994
  • 2 Beige J, Hohenbleicher H, Distler A, Sharma A M. G-Protein beta3 subunit C825T variant and ambulatory blood pressure in essential hypertension.  Hypertension. 33 1049-1051 1999; 
  • 3 Benjafield A V, Jeyasingam C L, Nyholt D R, Griffiths L R, Morris B J. G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension.  Hypertension. 32 1094-1097 1998; 
  • 4 Benjafield A V, Lin R C, Dalziel B, Gosby A K, Caterson I D, Morris B J. G-protein beta3 subunit gene splice variant in obesity and overweight.  Int J Obes Relat Metab Disord. 25 777-780 2001; 
  • 5 Brand E. et al. . The 825C/T polymorphism of the G-protein subunit beta3 is not related to hypertension.  Hypertension. 33 1175-1178 1999; 
  • 6 Buchmayer H. et al. . G-protein beta3 subunit gene (GNB3) polymorphism 825C → T in patients with hypertensive crisis.  Crit Care Med. 28 3203-3206 2000; 
  • 7 Dong Y. et al. . Association between the C825T polymorphism of the G protein beta3-subunit gene and hypertension in blacks.  Hypertension. 34 1193-1196 1999; 
  • 8 Gutersohn A, Naber C, Muller N, Erbel R, Siffert W. G protein β3 subunit 825 TT genotype and post-pregnancy weight retention.  Lancet. 355 1240-1241 2000; 
  • 9 Hebebrand J. et al. . Use of percentiles for the body mass index in anorexia nervosa: diagnostic, epidemiological and therapeutic considerations.  Int J Eat Dis. 19 359-369 1996; 
  • 10 Hegele R A, Anderson C, Young T K, Connelly P W. G-protein β3 subunit gene splice variant and body fat distribution in Nunavut Inuit.  Genome Res. 9 972-977 1999; 
  • 11 Hengstenberg C. et al. . Association between a polymorphism in the G protein beta3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction.  Cardiovasc Res. 49 820-827 2001; 
  • 12 Hinney A. et al. . Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.  Int J Obes Relat Metab Disord. 21 224-230 1997; 
  • 13 Hinney A. et al. . Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.  J Clin Endocrinol Metab. 84 1483-1486 1999; 
  • 14 Hocher B, Slowinski T, Stolze T, Pleschka A, Neumayer H H, Halle H. Association of maternal G protein β3 subunit 825T allele with low birthweight.  Lancet. 355 1241-1242 2000; 
  • 15 Kato N, Sugiyama T, Morita H, Kurihara H, Yamori Y, Yazaki Y. G protein beta3 subunit variant and essential hypertension in Japanese.  Hypertension. 32 935-358 1998; 
  • 16 Larson N, Hutchinson R, Boerwinkle E. Lack of association of 3 functional gene variants with hypertension in African Americans.  Hypertension. 35 1297-1300 2000; 
  • 17 Sasieni P. From genotypes to genes: doubling the sample size.  Biometrics. 53 1253-1261 1997; 
  • 18 Schunkert H. et al. . Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure levels.  Hypertension. 32 510-513 1998; 
  • 19 Siffert W. et al. . Association of a human G-protein beta3 subunit variant with hypertension.  Nat Genet. 18 45-48 1998; 
  • 20 Siffert W, Naber C, Walla M, Ritz E. G protein β3 subunit 825T allele and its potential association with obesity in hypertensive subjects.  J Hypertension. 17 1095-1098 1999a; 
  • 21 Siffert W. et al. . Worldwide ethnic distribution of the G protein β3 subunit 825T allele and its association with obesity in Caucasians, Chinese and Black African individuals.  J Am Soc Nephrol. 10 1921-1930 1999b; 
  • 22 Sina M. et al. . Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene.  Am J Hum Genet. 65 1501-1507 1999; 
  • 23 Tsai C H. et al. . G protein beta3 subunit variant and essential hypertension in Taiwan - a case-control study.  Int J Cardiol. 73 191-195 2000; 

Dr. Anke Hinney

Clinical Research Group

Department of Child and Adolescent Psychiatry

Schützenstr. 49

D-35039 Marburg

Germany

Phone: + 49-64 21-2 86 53 61

Fax: + 49-64 21-2 86 30 56

Email: Anke.Hinney@med.uni-marburg.de

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