| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q35.1 | {Hypertension, diastolic, resistance to} | 608622 | Autosomal dominant | 3 | KCNMB1 | 603951 |
A number sign (#) is used with this entry because of evidence that resistance to diastolic hypertension can result from variation in the gene encoding beta member 1 of subfamily M of the large conductance calcium-activated potassium channels (KCNMB1; 603951) on chromosome 5q35.
Hypertension is a significant risk factor for cardiac and renal disease, arteriosclerosis, retinopathy, and stroke. Systolic hypertension reflects an increase in the force of cardiac contraction, whereas diastolic hypertension reflects an increase in peripheral vascular resistance. Normalization of blood pressure is associated with reductions in morbidity and mortality related to end-organ damage.
By direct sequencing of the exons encoding the KCNMB1 gene in 11 severely hypertensive and 12 strictly normotensive individuals, Fernandez-Fernandez et al. (2004) identified a 352G-A transition in the third exon (603951.0001), corresponding to a glu65-to-lys (E65K) substitution. They screened a population sample of 3,876 randomly selected participants for this mutation and found genotype frequencies of 78.4% for EE homozygotes, 20% for EK heterozygotes, and 1.6% for KK homozygotes. The frequency of the E65K mutation (KK + KE) decreased with increasing diastolic blood pressure (DBP) values, from 21.6% in the normotensive group to 3.2% in the severely hypertensive group (p = 0.008). The age- and sex-adjusted ORs for K carriers with diastolic blood pressures greater than or equal to 105 mm Hg and 110 mm Hg were 0.39 (95% CI, 0.17-0.93, p = 0.034) and 0.12 (95% CI, 0.02-0.90, p = 0.039), respectively. The magnitude and direction of the associations were consistent with a protective effect of the K allele against the severity of diastolic hypertension and with a progressively deleterious effect of the EE genotype.
Fernandez-Fernandez, J. M., Tomas, M., Vazquez, E., Orio, P., Latorre, R., Senti, M., Marrugat, J., Valverde, M. A. Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension. J. Clin. Invest. 113: 1032-1039, 2004. [PubMed: 15057310] [Full Text: https://doi.org/10.1172/JCI20347]