A novel haplotype within C-reactive protein gene influences CRP levels and coronary heart disease risk in Northwest Indians

Abstract

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.

A transition of C to G (rs1800796) at promoter region of IL6 gene is associated with lowered risk of elevated blood glucose in rural Thais

“…In this study, we investigated whether polymorphisms rs2794521 of the CRP gene, rs1800796 of the IL6 gene and rs1799964 of the TNF gene are related to elevated blood glucose among the Thai population. Regarding the results, the distribution of each variant was consistent with previous studies [9,12,15,[19][20]. The wild type of each of the selected gene polymorphisms was most frequent, followed by the heterozygous variant, and nally the homozygous variant.…”

“…Polymorphisms located in promoter regions, including rs2794521 (-717 A/G) of CRP gene, -572 C/G (rs1800796) of IL6 gene and -1031 T/C (rs1799964) of TNF gene, have been associated with T2DM risk [7,[9][10][11][12][13]. Several studies demonstrated a notable in uence of the rs2794521 polymorphism on CRP secretion [14][15][16]. Alteration of CRP concentration may modify T2DM risk [5][6]9].…”

Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population

“…Several lines of evidence indicate that increased inflammatory cytokine levels and inflammatory cytokine activity detectable in peripheral blood have a prognostic role in predicting future cardiac events and clinical course (Tousoulis et al, 2006;De Gennaro et al, 2012). Recent studies have also shown that inflammationrelated genes might be correlated with CAD risk (Zakynthinos and Pappa, 2009;Shankar and Kakkar 2010;Li et al, 2012;Xie et al, 2012;Singh et al, 2014), thus aligning a number of inflammatory cytokines, their expression and their activity, as key mediators of CAD. Inflammatory pathways are mediated by proximal cytokines, such as Tumor Necrosis Factor-Alpha (TNF-α) and Tumour Necrosis Factor Beta (TNF-β)/Lymphotoxin Alpha) (LT-α), Interferon gamma (IFN-ɣ) and interleukin-6 (IL-6) which suggest they may influence CAD risk.…”

Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers

“…Although the CRP-717 T/C polymorphism is related to the development of acute and chronic inflammatory processes 6,7,11 , few studies have evaluated this genetic polymorphism in infectious processes 8,9,12 . In Hepatitis B virus (HBV) infection, CRP-717 T/C polymorphism evaluation has been restricted to the Asian population 8,9 .…”