Mutations of the -Adrenergic Receptor Gene

  The structure gene of nine subjects was scrutinized. Three candidates had developed essential hypertension. They were compared to three non-hypertensive subjects of the same family. Another comparison was made between a known salt sensitive subject and two salt resistant ones[18].

One single base substitution leading to an amino acid change was found at position 1309 (amino acid 16), changing glycine to arginine (see figure fig:1309). In the 2ar, amino acid 16 is located in the extracellular amino terminus, next to a glycosylation site (see figure figrecstruct). The other mutations found were silent ones, possibly altering the mRNA stability. Especially the mutation at position 1515 (see figure fig:1515), encodes for an amino acid in one of the highly conserved regions of the human adrenergic receptor (membrane spanning domain II). The amino acid of the mutation at position 1786 is situated at the edge of membrane spanning domain III and extracellular loop II (see figure fig:1786), whereas the mutations at position 2316 and 2502 (see figure fig:2316) are located at the C-terminus of the receptor.

The found base substitutions were sequenced from 10 to 20 different clones for each subject, which made it possible to reveal heterozygous subjects for the mutations at 1309, 2316 and 2502. This led to the formulation of four different alleles   for the human -adrenergic receptor, as outlined in table tab:alleles. The 2ar sequence, protein translation and found mutations are summarized in table tab:seq.

 
Table 3.4: Alleles of the human adrenergic receptor 

 
Figure 3.5: The amino acid changing mutation found at position 1309 on the left side compared to the wild type (right picture) 

 
Figure 3.6: The point mutation at position 1515 (left side) compared to the published wild type (right side) 

 
Figure 3.7: The point mutation at position 1786 of the human -adrenergic receptor 

 
Figure 3.8: The point mutation at position 2316 of the human -adrenergic receptor 

 
Table 3.5: Nucleotide sequence of the human -adrenergic receptor gene