Genetic Factors Contributing to Hypertension. With Emphasis on Hypertension in Type 2 Diabetes

Abstract: The causes of hypertension (HT) and type 2 diabetes (T2DM) are mainly unknown, but they arise from interplay between several genetic and environmental factors. The aim of this thesis was to investigate whether polymorphisms in putative candidate genes for HT increase the susceptibility to HT and/or T2DM. The DD genotype of the angiotensin converting enzyme (ACE) gene I/D polymorphism was associated with HT in a large population-based study from Skara, Sweden, particularly with HT combined with T2DM in lean patients less than 70 years. Further, the D allele increased mortality in male patients with HT and T2DM. Three polymorphisms in the angiotensinogen gene were not found to be associated with HT and/or T2DM. A novel association between hypertension and the Arg389Arg genotype of the Arg389Gly polymorphism in the beta 1 adrenergic receptor (B1AR) gene was shown in a case-control study from southern Sweden. The Arg389Arg genotype conferred higher diastolic blood pressure levels and increased heart rate in genotype discordant sibling pairs from Finland. Finally, the Arg16 and Gln27 alleles of the Arg16Gly and Gln27Glu polymorphisms in the beta 2 adrenergic receptor (B2AR) gene were shown to be associated with hypertension combined with T2DM. The Arg16 allele conferred higher systolic blood pressure levels and higher body mass index in genotype discordant sibling pairs. In conclusion, the ACE gene DD genotype increases the susceptibility to HT and ID and DD genotypes confer an increased risk of mortality. Genetic variants of B1AR and B2AR genes influence blood pressure and increase susceptibility for HT.