Publications

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men
Firouzi M, Kok B, Spiering W, Busjahn A, Bezzina CR, Ruijter JM, Koeleman BP, Schipper M, Groenewegen WA, Jongsma HJ, de Leeuw PW
J Hypertens. 2006 Feb;24(2):325-30.
Abstract:

OBJECTIVE: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals.
METHODS: Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic).
RESULTS: We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033).
CONCLUSION: These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in men.

Heritability of free and receptor-bound leptin in normal twins
Jordan J, Brabant G, Brinsuk M, Tank J, Horn R, Luft FC, Busjahn A
Am J Physiol Regul Integr Comp Physiol. 2005 May;288(5):R1411-6
Abstract:

Free and receptor-bound leptin may be regulated by different mechanisms. Genes that influence the concentration of these fractions may have an important functional bearing. We determined circulating leptin receptor concentrations, bound as well as free leptin concentrations, and body composition in 24 monozygotic (MZ) and in 22 dizygotic (DZ) twin pairs. Bound leptin and leptin receptor concentrations were inversely correlated with body fat content. Free leptin concentrations were directly correlated with body fat content. The correlations in age- and sex-adjusted free leptin, bound leptin, and leptin receptor concentrations were higher between MZ twins than between DZ twins. Adjusted heritability (h2) estimates were 0.28 for free leptin, 0.73 for bound leptin, and 0.55 for leptin receptor. The genetic correlation with body fat was -0.58 for the leptin receptor, -0.20 for bound leptin, and 0.93 for free leptin. Our data are consistent with a strong genetic influence on leptin receptor and bound leptin and a weaker genetic influence on free leptin concentrations. The same genes that lower bound leptin and leptin receptor concentrations may increase fat mass or vice versa.

Single nucleotide polymorphism map of five long-QT genes
Aydin A, Bahring S, Dahm S, Guenther UP, Uhlmann R, Busjahn A, Luft FC.
J Mol Med. 2005 Feb;83(2):159-65
Abstract:

We screened a white population for single nucleotide polymorphisms (SNPs) in five long QT syndrome genes, namely, KCNQ1 (LQT1), HERG (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). We found 35 SNPs, 10 of which have not been previously described. Ten SNPs were in KCNE1, six in HERG, eight in KCNQ1, four in KCNE2, and seven in SCN5A. Four SNPs were associated with QTc interval in our 141 subjects, one in KCNE1, one in KCNE2, and two in SCN5A. Two of these SNPs have not been described. We conclude that these five long QT syndrome genes contain common variants, some of which are associated with QTc interval in normal persons. We suggest that analysis of these SNPs in a much larger cohort would enable establishment of common haplotypes that are associated with QTc. These haplotypes could facilitate prediction of arrhythmia risk in the general population.

Pages