CACNB2基因多态性与原发性高血压的关联性研究

Association between CACNB2 gene polymorphisms and essential hypertension

目的探讨钙离子通道G2亚基基因（calciumchannelt72gene，CACNB2）多态性与温州汉族人群原发性高血压的相关性及应用荧光素酶报告基因技术检测rs7069292不同等位基因对基因表达的影响。方法收集原发性高血压患者637例，以血压正常者600名作对照，采用飞行时间质谱分型技术对CACNB2基因rs2228645、rs2357928、rs7069292、rs7099380、rs10764319和rs11014166共6个SNP位点进行分型。构建CACNB2基因5’上游-2831bp到-2460bp的rs7069292的侧翼序列的荧光素酶报告基因载体。结果高血压组rs7069292CT基因型频率及C等位基因频率高于正常对照组（5．20％vs．2．17％，2．59％vs．1．08％，均P〈0．05），分型未发现rs7069292CC基因型；含rs7069292C等位基因的启动子活性与T等位基因相比明显增高，差异有统计学意义（P〈0．05）；其余5个SNP位点各基因型频率及等位基因频率与对照组比较差异均无统计学意义（均P〉0．05）。结论CACNB2基因rs7069292多态性与温州汉族人群原发性高血压病有关联，T〉C变异可能是CACNB2基因功能表达的一个影响因子。

Objective To assess the association between single nucleotide polymorphisms （SNPs） of calcium channel β2 subunit （CACNB2） gene and essential hypertension （EH） in ethnic Han Chinese in Wenzhou area, and to study the influence of rs7069292 alleles on gene expression with luciferase reporter technique. Methods Sixty hundred and thirty seven Han Chinese with EH and 600 normal controls were enrolled. Genotypes of 6 SNP within CACNB2 gene including rs2228645, rs2357928, rs7069292, rs7099380, rs10764319 and rs11014166 were determined with matrix assisted laser desorption ionization/ time of flight mass spectrometer （MALDI-TOF MS）. A luciferase reporter gene plasmid containing the fragment flanking rs7069292 （-2831 bp to -2460 bp） in the 5＇ regulatory region of CACNB2 was constructed. Results Compared with the control, CT and TT genotypes for the rs7069292 locus were significantly more common in EH group （5.20% vs. 2.17% ,2.59% vs. 1.08%, P〈0.05）. CC genotype was not found. Promoter activity for allele C of the rs7069292 locus was significantly increased compared with allele T （P〈0.05）. No significant difference was detected for other 5 SNPs in terms of genotypes and allele frequency. Conclusion The rs7069292 CT polymorphism of the CACNB2 gene is associated with EH in ethnic Han Chinese from Wenzhou area. A T〉C mutation may affect the expression of CACNB2.