Peroxisome proliferator-activated receptor gamma gene locus is related to body mass index and lipid values in healthy nonobese subjects
Knoblauch-H; Busjahn-A; Muller-Myhsok-B; Faulhaber-HD; Schuster-H; Uhlmann-R; Luft-FC
Arterioscler Thromb Vasc Biol 1999 Dec;19(12):2940-4

The peroxisome proliferator-activated receptor gamma (PPARgamma) gene has been implicated in morbid obesity and is important to lipid and carbohydrate metabolism. However, the relevance of gene variations in healthy nonobese subjects has not been defined. We recruited monozygotic and dizygotic healthy nonobese twin subjects to test the hypothesis that the PPARgamma gene is important to body mass index and lipid concentrations in healthy nonobese subjects. Both linkage and association strategies were used in the same dizygotic twins. The PPARgamma gene locus was linked (P<0.01) to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index as quantitative traits. A biallelic variant in the PPARgamma gene was associated with high-density lipoprotein cholesterol and body mass index (P<0.05). We also looked for linkage between the same variables and the retinoic X receptor gene locus. This locus was linked to total and low-density lipoprotein cholesterol as well as triglycerides. We conclude that the PPARgamma gene is highly relevant to lipid metabolism and body mass index, not only in the morbidly obese but also in healthy nonobese subjects. The same appears to be true for its binding partner. Sequencing these genes in twins would serve to identify gene variations contributing to body mass index and lipid concentrations in healthy nonobese subjects.

Linkage but lack of association for blood pressure and the a-adducin locus in normotensive twins
Busjahn A,Aydin A, von Treuenfels N, Faulhaber H-D, Gohlke H-R, Knoblauch H, Schuster H, and Luft FC
J. Hypertens. 1999; 10: 1437-1441

Background a-adducin is a cytoskeletal protein involved with sodium-pump activity in the renal tubule. The a-adducin gene locus has been linked to hypertension and a polymorphism identified which is associated with hypertension; however, the role of the a-adducin gene locus in normal blood pressure regulation is not defined. We performed a combined linkage and association study in normotensive MZ and DZ twins and their parents to address this issue.
Methods We studied 126 MZ and 70 DZ twin pairs and parents of DZ twins. Blood pressure and cold-pressor blood pressure values were obtained. Cardiac dimensions were measured echocardiographically. Three microsatellites adjacent to the a-adducin gene were studied as well as the 460 Trp mutation in the a-adducin gene. Results We obtained strong evidence for linkage (p<0.001) between the a-adducin gene locus and systolic blood pressure. However, we were not able to associate the 460 Trp mutation with higher blood pressures, cold-pressor responses, or cardiac dimensions.
Conclusions The a-adducin gene locus is relevant to blood pressure regulation in normal subjects. Failure to find association between higher blood pressures and the 460 Trp mutation suggests that this mutation may become important only when hypertension is triggered, or that other variations in a-adducin are present which have not yet been discovered.

Quantitative trait loci for blood pressure exist near the IGF-1, the Liddle syndrome, the angiotensin II-receptor gene and the renin loci in man
Nagy-Z; Busjahn-A; Bahring-S; Faulhaber-HD; Gohlke-HR; Knoblauch-H; Rosenthal-M; Mller-Myhsok-B; Schuster-K; Luft-FC

Blood pressure (BP) is heritable and finding quantitative trait loci that influence BP is an important step in identifying genes responsible for BP regulation. Sixty-six pairs of dizygotic (DZ) twin subjects and their parents were used in a sib-pair analysis to look for linkage of selected candidate genes to the quantitative trait BP. Microsatellite markers were tested in the vicinity of the gene loci for insulin-like growth factor-1 (IGF-1), Liddle syndrome, autosomal-dominant hypertension with brachydactyly, angiotensinogen, angiotensin II type I receptor, angiotensin-converting enzyme, renin, and lipoprotein lipase. BP was measured in a standardized manner. Heart size was determined echocardiographically. Significant linkage was found at the IGF-1, Liddle syndrome, and AT(1) receptor gene for systolic BP. Linkage for diastolic BP was found at the autosomal-dominant hypertension with brachydactyly locus. Both systolic and diastolic BP were linked to the renin gene locus. The linkage was most consistent for the IGF-1 gene locus and systolic Bg. Linkage was also found between the IGF-1 gene locus and posterior cardiac wall thickness, septal thickness, and left ventricular mass index. It is suggested that these quantitative trait loci may be important for the subsequent detection of allelic variants for elevated BP. Furthermore, these results linking the IGF-1 gene locus to both BP and cardiac dimensions underscore the importance of the IGF-1 gene as a candidate gene for cardiovascular disease.