No association with hypertension of CLCNKB and TNFRSF1B polymorphisms at a hypertension locus on chromosome 1p36

OBJECTIVE: Chromosome 1p36 has been linked to essential hypertension and systolic blood pressure. This locus contains the chloride channel-Kb gene (CLCNKB) and the tumour necrosis factor receptor 2 gene (TNFRSF1B). Polymorphisms of each of these have shown association with hypertension, and a CLCNKB T481S variant alters receptor function. Here we performed association studies in a well-characterized cohort of hypertensives and normotensives whose blood pressure status matched that of both their parents. METHODS: The study involved 196 essential hypertensives and 321 normotensives. These were genotyped for TNFRSF1B variants T-1710A upstream, A257G in exon 2, a CA-repeat polymorphism in intron 4, E232K and M196R in exon 6, and T1668G and T1690C in the 3'-untranslated region, and the T481S variant of CLCNKB. RESULTS: The CLCNKB T481S variant showed no association with hypertension. Thermodynamic modelling of the 3'-untranslated region of TNFRSF1B mRNA predicted that the T1668G variant alters the stem-loop structure and thus the mRNA stability and expression. However, neither this nor the other TNFRSF1B polymorphisms, either alone or after haplotype analysis, were associated with hypertension. Moreover, for each gene the blood pressure, body mass index, plasma sodium and plasma lipid concentrations were generally similar across genotypes. CONCLUSION: Our data fail to support previous association findings for TNFRSF1B and CLCNKB at the chromosome 1p36 locus implicated in hypertension.