A LINKAGE AND CROSS-SECTIONAL STUDY OF HYPERTENSION AND OBESITY USINGA POLY(A) ALU REPEAT POLYMORPHISM AT THE GLUCAGON RECEPTOR GENE LOCUS(17Q25)

1. Previous glucagon receptor gene (GCGR) studies have shown a Gly40Se r mutation to be more prevalent in essential hypertension and to affec t glucagon binding affinity to its receptor. An Alu-repeat poly(A) pol ymorphism colocalized to GCGR was used in the present study to test fo r association and linkage in hypertension as well as association in ob esity development. 2. Using a cross-sectional approach, 85 hypertensiv es and 95 normotensives were genotyped using polymerase chain reaction primers flanking the Alu-repeat, Both hypertensive and normotensive p opulations were subdivided into lean and obese categories based on bod y mass index (BMI) to determine involvement of this variant in obesity . For the linkage study, 89 Australian Caucasian hypertension affected sibships (174 sib-pairs) were genotyped and the results were analysed using GENE-HUNTER, Mapmaker Sibs, ERPA and SPLINK (all freely availab le from http://linkage.rockefeller.edu./soft/list.html). 3. Cross-sect ional results for both hypertension and obesity were analysed using Ch i-squared and Monte Carlo analyses. Results did not show an associatio n of this variant with either hypertension (chi(2) = 6.9, P = 0.14; Mo nte 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 i ndicate linkage of the poly(A) repeat with hypertension. Hence, result s 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 d raw definitive conclusions.