RESUMO
BACKGROUND: The band 9p21.3 contains an established genomic risk zone for cardiovascular disease (CVD). Since the initial 2007 Wellcome Trust Case Control Consortium study (WTCCC), the increased CVD risk associated with 9p21.3 has been confirmed by multiple studies in different continents. However, many years later there was still no confirmed report of a corresponding association of 9p21.3 with hypertension, a major CV risk factor, nor with blood pressure (BP). THEORY: In this contribution, we review the bipartite haplotype structure of the 9p21.3 risk locus: one block is devoid of protein-coding genes but contains the lead CVD risk SNPs, while the other block contains the first exon and regulatory DNA of the gene for the cell cycle inhibitor p15. We consider how findings from molecular biology offer possibilities of an involvement of p15 in hypertension etiology, with expression of the p15 gene modulated by genetic variation from within the 9p21.3 risk locus. RESULTS: We present original results from a Colombian study revealing moderate but persistent association signals for BP and hypertension within the classic 9p21.3 CVD risk locus. These SNPs are mostly confined to a 'hypertension island' that spans less than 60 kb and coincides with the p15 haplotype block. We find confirmation in data originating from much larger, recent European BP studies, albeit with opposite effect directions. CONCLUSION: Although more work will be needed to elucidate possible mechanisms, previous findings and new data prompt reconsidering the question of how variation in 9p21.3 might influence hypertension components of cardiovascular risk.
RESUMO
As there is controversy about the prevalence of hypertension in patients with polycystic ovary syndrome (PCOS) and, up to the present moment, no studies have evaluated the impact of body mass index (BMI) on blood pressure levels (BP) in these patients, we studied retrospectively sixty-nine patients with PCOS, with BMI of 29.0 ± 6.7 kg/m² and aged 25.6 ± 5.6 yr, subdivided into three groups according to BMI (normal, overweight and obese) and evaluated regarding BP (mercury sphygmomanometer), basal hormonal profile, fasting glucose, and insulin sensitivity (HOMA-IR). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were normal (118.1 ± 17.0 and 74.7 ± 11.5 mmHg, respectively), with a hypertension prevalence of 20.3 percent. Of these patients, 78.6 percent were obese and 21.4 percent were overweight. When the groups were compared according to BMI, a significant increase in SBP and DBP was observed (higher in overweight and obese patients for SBP and higher in obese for DBP), as well as a significant progressive increase in glucose, insulin, homeostatic model assessment, and a significant progressive decline in LH levels. When the patients were subdivided as normotensive or hypertensive, a significant difference was observed only for BMI (28.2 ± 6.1 and 34.7 ± 8.6 kg/m², respectively; p = 0.007). In conclusion, we observed a significant and progressive impact of BMI on blood pressure levels in our patients with polycystic ovary syndrome.
Como há controvérsia sobre a prevalência de hipertensão arterial em pacientes com a síndrome dos ovários policísticos (SOP) e, até o momento, nenhum estudo avaliou o impacto do índice de massa corporal (IMC) sobre a pressão arterial (PA), foram estudados retrospectivamente 69 pacientes com a SOP, com IMC de 29,0 ± 6,7 kg/m² e idade de 25,6 ± 5,6 anos, subdivididos em 3 grupos de acordo com o IMC (normal, sobrepeso e obesos) e avaliados com relação à PA, perfil hormonal basal, glicemia de jejum e sensibilidade à insulina (HOMA-IR). As médias das pressões arteriais sistólica (PAS) e diastólica (PAD) foram normais (118,1 ± 17,0 e 74,7 ± 11,5 mmHg, respectivamente), com uma prevalência de hipertensão de 20,3 por cento. Das pacientes hipertensas, 78,6 por cento eram obesas e 21,4 por cento apresentavam sobrepeso. Quando os grupos, subdivididos de acordo com o IMC, foram comparados, aumento significativo da PAS e PAD foi observado (PAS maior nas pacientes com sobrepeso e obesas e PAD maior nas pacientes obesas), assim como um aumento progressivo da glicemia, insulina e HOMA-IR, e um decréscimo significante e progressivo de LH. Quando as pacientes foram subdivididas em normotensas e hipertensas, diferença significativa foi observada somente para IMC (28,2 ± 6,1 e 34,7 ± 8,6 kg/m², respectivamente; p = 0,007). Em conclusão, observamos um impacto significativo e progressivo do IMC sobre os níveis pressóricos em nossas pacientes com a síndrome dos ovários policísticos.