A linkage and cross-sectional study of hypertension and obesity using a poly (A) Alu-repeat polymorphism at the glucagon receptor gene locus (17q25).
1. Previous glucagon receptor gene (GCGR) studies have shown a Gly40Ser mutation to be more prevalent in essential hypertension and to affect glucagon binding affinity to its receptor. An Alu-repeat poly(A) polymorphism colocalized to GCGR was used in the present study to test for association and linkage in hypertension as well as association in obesity development. 2. Using a cross-sectional approach, 85 hypertensives and 95 normotensives were genotyped using polymerase chain reaction primers flanking the Alu-repeat. Both hypertensive and normotensive populations were subdivided into lean and obese categories based on body mass index (BMI) to determine involvement of this variant in obesity. For the linkage study, 89 Australian Caucasian hypertension affected sibships (174 sibpairs) were genotyped and the results were analysed using GENEHUNTER, Mapmaker Sibs, ERPA and SPLINK (all freely available from http:@linkage.rockefeller.edu./soft/list.hmtl). 3. Cross-sectional results for both hypertension and obesity were analysed using Chi-squared and Monte Carlo analyses. Results did not show an association of this variant with either hypertension (chi(2) = 6.9, P = 0.14; Monte Carlo chi(2) = 7.0, P = 0.11; n = 5000) or obesity (chi(2) = 3.3, P = 0.35; Monte Carlo chi(2) = 3.26, P = 0.34; n = 5000). In addition, results from the linkage study using hypertensive sib-pairs did not indicate linkage of the poly(A) repeat with hypertension. Hence, results did not indicate a role for the Alu-repeat in either hypertension or obesity. However, as the heterozygosity of this poly(A) repeat is low (35%), a larger number of hypertensive sib-pairs may be required to draw definitive conclusions.
Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia.
S
S
Rutherford
S D
SD
Boatwright
G A
GA
Samwell
B J
BJ
Morris
L R
LR
Griffiths
D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006949:Hyperlipidemias / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics*; D017566:Microvascular Angina / Q000503:physiopathology; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011061:Poly A / Q000235:genetics*; D011110:Polymorphism, Genetic; D018027:Receptors, Glucagon / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
D005819:Genetic Markers; D018027:Receptors, Glucagon; D011061:Poly A; D004247:DNA