Polymorphisms in angiotensinogen gene (M235T and G(-6)A) in multifactorial diseases.

The aim of the study is to compare results of three association (case-control) studies in three multifactorial disorders (essential hypertension, atopic diseases and psoriasis) with two polymorphisms of angiotensinogen gene (M235T and A(-6)G). The diseases were chosen for their multigenic base and different immunological characteristic (Th1, Th2 and Thps) and angiotensinogen gene for its pleiotropic functional effects in general adaptive reactions. In all (control as well as case) groups, tight linkage disequilibrium between the polymorphisms was found. The strength of linkage (%) differed among the group. The direction of the linkage is identical in all groups (T is combined with A, M is combined with G). In hypertensive-normotensive study, only Hardy-Weinberg disequilibria were found, especially in men. No case-control differences were found for either single alleles or for allelic concurrence of both polymorphisms. In atopy-control study, marginal case-control differences in single allele distribution of both polymorphisms were found, but only in women. In psoriasis-control study, the only significant case-control difference was found,when genotypes MTAA and MTGG were present in 2/136 psoriatic patients vs. 20/142 control subjects (OR 0.1, 95% confidence interval 0.02-0.42, P=0.00015). The frequent polymorphisms in pleiotropic genes can form different formulae of genotype distribution in different multigenic diseases according to their contribution to the onset and/or progression of the disease in some evolutionary consequences.