Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population.

Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population.
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DOI:
10.1371/journal.pone.0077562
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Ruiz-Opazo N
Ruiz-Opazo N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Glorioso N;Herrera VL;Didishvili T;Ortu MF;Zaninello R;Fresu G;Argiolas G;Troffa C;Ruiz-Opazo N

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冠状动脉疾病、心力衰竭、致命性心律失常、中风和肾脏疾病是人类最常见的死亡原因,原发性高血压仍然是主要的风险因素。原发性高血压的易感基因的阐明一直是困难的,因为它的复杂性,多因素的性质涉及遗传,环境,性别和年龄依赖性的性质。我们调查是否11p15.5区域同线大鼠1号染色体区域含有多个血压数量性状基因座(QTL)检测达尔大鼠intercrosss港口多态性,有助于易感性/耐原发性高血压在撒丁岛人口。使用跨越11p15.5的18 Mb的微卫星标记进行的初步测试检测到D11 S1318(在2.1 Mb,P = 0.004)和D11 S1346(在10.6 Mb,P = 0.0000004)之间的强关联,这表明这些标记附近的位点可能有助于我们的撒丁岛队列的易感性。NLR家族、含pyrin结构域6/血管紧张素-加压素受体(NLRP 6/AVR)和肾上腺髓质素(ADM)分别与D11 S1318和D11 S1346非常接近;因此,我们在撒丁岛队列中检测了NLRP 6/AVR和ADM内的单核苷酸多态性(SNP)与高血压的相关性。根据性别分层,我们检测到一个NLRP 6/AVR SNP与男性高血压易感性降低相关(rs7948797 G,P = 0.029; OR = 0.73 [0.57-0.94])。对于ADM,性别特异性分析显示rs 4444073 C仅在男性人群中与原发性高血压易感性增加显著相关(P = 0.006; OR = 1.44 [1.13-1.84])。我们的研究结果显示NLRP 6/AVR和ADM基因座与男性原发性高血压相关,提示存在性别特异性NLRP 6/AVR和ADM变异体影响男性原发性高血压的易感性。
Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL) detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004) and D11S1346 (at 10.6 Mb, P = 0.00000004), suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR), and adrenomedullin (ADM) are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs) within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57–0.94]). For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13–1.84]). Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension.
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发表时间: 2005-12-30
期刊: BMC GENETICS
影响因子: 2.9
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