Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians

Previous studies have suggested that the Trp460 allele of the Gly460Trp pol ymorphism in the Lu-adducin gene is associated with salt sensitivity and pr imary hypertension. The present study was undertaken to evaluate if the Trp 460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertensio n and 265 normotensive control subjects from Sweden were examined and genot yped for the Gly460Trp polymorphism using polymerase chain reaction and res triction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subject s from Finland to replicate the findings. The frequency of the Trp460 allel e was lower in hypertensive patients than in normotensive controls in the S wedish population (17.7% vs 23.0%; P = 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in whic h the frequency of the Trp460 allele was significantly lower in hypertensiv e patients than in normotensive controls (17.0% vs 21.7%; P = 0.02). In sub jects who did not receive antihypertensive medication (n = 447) there was n o difference between carriers of the three different codon 460 genotypes (T rp-Trp; Trp-Gly and Gly-Gly) either for systolic (128 +/- 18; 127 +/- 15 an d 129 +/- 17 mm Hg, NS) or for diastolic blood pressure (75.6 +/- 12.1; 74. 7 +/- 9.3 and 75.0 +/- 10.4 mm Hg, NS). In conclusion, the lower frequency of the Trp460 allele in hypertensive patients than in normotensive controls strongly argues against a pathogenic role of this allele in primary hypert ension. The results rather suggest that another variant in linkage disequil ibrium with the Gly460Trp polymorphism increases susceptibility for hyperte nsion.