4.3 Article Proceedings Paper

Sex, genes and blood pressure

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BLACKWELL PUBLISHING ASIA
DOI: 10.1046/j.1440-1681.2001.03579.x

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androgen; aromatase; oestrogen; receptor; 5 alpha-reductase; sex differences; sex steroids; X chromosome; Y chromosome

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1. Throughout most of life, males have higher average blood pressures than females. This sexual dichotomy may be related to genetic factors including the X and Y sex chromosomes and genes that control sex steroids. Resultant physiological differences between men and women may also be relevant to the quantitative variation of blood pressure within the sexes. 2. The present overview collates our published and novel sex-related genetic data in relation to blood pressure from the Victorian Family Heart Study. These include a multipoint quantitative linkage analysis of the X chromosome and genetic association studies of single nucleotide polymorphisms (SNP) of the Y chromosome and genes encoding the androgen receptor (AR), oestrogen receptor alpha (ERalpha), 5alpha-reductase types I and II (SRD5A1 and SRD5A2) and aromatase (CYP19). 3. Systolic blood pressure (SBP) was linked (Z = 3.3, genome-wide P < 0.05) to a region of the X chromosome that encompassed the AR gene and the Y chromosome was associated with diastolic blood pressure (DBP; P = 0.03). In new analyses, we observed a possible association between a SNP in AR and DBP in 369 males (84.5 vs 82.1 mmHg for genotype A vs genotype B, respectively; P = 0.06) and a significant association between haplotypes of the Y chromosome and AR SNP in males (P = 0.01) with a difference of nearly 6 mmHg DBP between extreme groups. Associations were also observed for polymorphisms of SRD5A1 and ERα with DBP and SBP in males, respectively. 4. The findings indicate that genes related to sexual phenotypes may be relevant to the normal variation in blood pressure, even within the sexes. Further genetic and physiological analyses will be required to confirm these observations and to determine the mechanisms of action and the nature of any interactions.

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