Speirs Helen J L, Katyk Ksenia, Kumar Natasha N, Benjafield Adam V, Wang William Y S, Morris Brian J
Basic & Clinical Genomics Laboratory, School of Medical Sciences and Institute for Biomedical Research, The University of Sydney, Sydney, NSW 2006, Australia.
J Hypertens. 2004 May;22(5):931-6. doi: 10.1097/00004872-200405000-00014.
To perform association studies of polymorphisms of the potential candidate essential hypertension (HT) genes GRK4, PTP1B and HSD3B1.
Subjects consisted of 168 unrelated, Caucasian essential hypertensive (HT) patients and 312 normotensive (NT) controls. Biological power was increased by ensuring subjects in each group had parents with the same blood pressure (BP) status as theirs. Three GRK4gamma variants (R65L, A142V and A486V), one HSD3B1 variant (T<---C Leu) and one PTP1B variant (1484insG) were genotyped by polymerase chain reaction and restriction enzyme digestion or by homogenous MassEXTEND Assay.
The V allele of the A486V variant of GRK4gamma, but not the R65L or A142V variants, showed an association with HT (P = 0.02). The V allele was also associated with an elevation in systolic blood pressure (SBP) (P = 0.002). Although the L65 and the V142 alleles tracked with elevation in diastolic (DBP), this was seen only in male HTs (P = 0.009; P = 0.002, respectively). Haplotype frequencies differed between the HT and NT groups, particularly for the R, V, V haplotype combination of R65L, A142V and A486V, respectively. Neither of the HSD3B1 or PTP1B variants were associated with HT.
Genetic variation in GRK4gamma was associated with HT in the subjects studied.
对潜在的候选原发性高血压（HT）基因GRK4、PTP1B和HSD3B1的多态性进行关联研究。
研究对象包括168名无亲缘关系的白种人原发性高血压（HT）患者和312名血压正常（NT）的对照者。通过确保每组受试者的父母具有与其相同的血压（BP）状态来提高统计学效能。采用聚合酶链反应和限制性内切酶消化或同质MassEXTEND分析对GRK4γ的三个变体（R65L、A142V和A486V）、一个HSD3B1变体（T<---C Leu）和一个PTP1B变体（1484insG）进行基因分型。
GRK4γ的A486V变体的V等位基因与HT相关，而R65L或A142V变体则不然（P = 0.02）。V等位基因还与收缩压（SBP）升高相关（P = 0.002）。虽然L65和V142等位基因与舒张压（DBP）升高相关，但仅在男性HT患者中观察到（分别为P = 0.009；P = 0.002）。HT组和NT组之间的单倍型频率不同，特别是分别针对R65L、A142V和A486V的R、V、V单倍型组合。HSD3B!或PTP1B变体均与HT无关。
在所研究的受试者中，GRK4γ的基因变异与HT相关。
