Singh Puneetpal, Singh Monica, Nagpal Harinder Singh, Kaur Taranpal, Khullar Shallu, Kaur Gurpreet, Dhillon Harjot, Di Napoli Mario, Mastana Sarabjit
Molecular Genetics Laboratory, Department of Human Genetics, Punjabi University, Patiala, 147002, Punjab, India,
Mol Biol Rep. 2014 Sep;41(9):5851-62. doi: 10.1007/s11033-014-3459-0. Epub 2014 Jun 26.
According to several epidemiological and clinical studies, the concentration of C-reactive protein (CRP) in blood is associated with the risk of coronary heart disease (CHD). However, these studies are limited in high incidence and prevalence area of North-West India. The present case control study investigated the contribution of three relevant CRP single nucleotide polymorphisms: -717A>G located in the promoter region (rs2794521), +1059G>C on exon2 (rs1800947) and +1444C>T in the 3' UTR (rs1130864) in 180 angiographically verified CHD cases and 175 control subjects. Minor allele frequencies (G, C and T) of rs2794521, rs1800947 and rs1130864 are observed to be 21.1, 11.7, 29.4 and 11.4, 10.0, 19.7 % in CHD cases and controls respectively. AA genotype of -717A>G and TT genotype of +1444C>T were significantly associated (P = 0.02 & 0.03 respectively) with the risk of CHD whereas, +1059G and +1444T were found to be strongly related (P = 0.023 & P = 0.008 respectively) with multivariable adjusted CRP levels. AGT Haplotype was significantly associated with the adjusted CRP levels (P < 0.05). Disease association analysis revealed that haplotype AGT influences CHD risk (OR 2.4, 95 % CI 1.23-4.84, P = 0.006) which exacerbates after correcting the confounding effects of risk variables (OR 2.5, 95 % CI 1.27-4.99, P = 0.004). With the global index of Akaike information criterion, it has been observed that the carrying each single unit of this susceptibility haplotype increases CHD risk by a value of 2.41 ± 0.439 (β ± SE) in the recessive mode.
根据多项流行病学和临床研究，血液中C反应蛋白（CRP）的浓度与冠心病（CHD）风险相关。然而，这些研究在印度西北部高发病率和高患病率地区存在局限性。本病例对照研究调查了三个相关CRP单核苷酸多态性的作用：位于启动子区域的-717A>G（rs2794521）、外显子2上的+1059G>C（rs1800947）以及3'非翻译区的+1444C>T（rs1130864），研究对象为180例经血管造影证实的冠心病患者和175名对照者。观察到rs2794521、rs1800947和rs1130864的次要等位基因频率（G、C和T）在冠心病患者和对照者中分别为21.1%、11.7%、29.4%和11.4%、10.0%、19.7%。-717A>G的AA基因型和+1444C>T的TT基因型分别与冠心病风险显著相关（P分别为0.02和0.03），而+1059G和+1444T被发现与多变量校正后的CRP水平密切相关（P分别为0.023和0.008）。AGT单倍型与校正后的CRP水平显著相关（P<0.05）。疾病关联分析显示，单倍型AGT影响冠心病风险（比值比2.4，95%置信区间1.23 - 4.84，P = 0.006），在校正风险变量的混杂效应后风险加剧（比值比2.5，95%置信区间1.27 - 4.99，P = 0.004）。根据赤池信息准则的全局指数，观察到在隐性模式下，携带这种易感单倍型的每个单位会使冠心病风险增加2.41±0.439（β±标准误）。
