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Surprising Interaction Between Genes, Gender, and Hypertension

ments. For example, men normally have slightly higher BP readings than women.

Accounting for these differences, the researchers set out to test their hypothesis that the influence of genes on blood pressure and hypertension varies with a patient’s gender. Ernst Beutler, M.D., of The Scripps Research Institute Department of Molecular and Experimental Medicine, organized a blood sample collection over a two-year period in order to prepare genomic DNA from the patients’ white blood cells. The researchers then focused on the genetic profiles, or genotypes, of more than 1,200 men and women whose systolic (the higher number in a BP reading) and diastolic (lower number) measurements fell at the extreme – highest and lowest – percentiles of distribution.

The study yielded 48 different genetic variations, or polymorphisms, on 35 different genes that encode proteins involved in blood pressure regulation. Thirty-three of the genes were on autosomes (chromosomes found in both sexes), and two were on the “X-linked” or sex chromosomes.

“Of the 35 genes, we found six genes that were quite different in the frequency of variation between people of either sex who had extremely high or low blood pressure,” said O’Connor.

Several diseases are caused by a variation on a single gene on the chromosome, called a single nucleotide polymorphism (SNP, pronounced “snip”). Examples of so-called SNP diseases are sickle-cell anemia and Huntington’s disease, where a single variant or mutation has a dramatic effect.

In contrast to these single-gene-specific diseases, the UCSD researchers observed more subtle variants on six different genes, indicating that multiple genes can contribute to high blood pressure. “We discovered that there’s more than one gene at work in hypertension,” said O’Connor, adding that the team was surprised to find that these SNPs appear to affect men and women differently.

Among the gene variants, each w
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