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.
Key words:
Association - underweight - obesity - GNB3 - 825-T allele
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
Telefon: + 49-64 21-2 86 53 61
Fax: + 49-64 21-2 86 30 56
eMail: Anke.Hinney@med.uni-marburg.de