TGFB1 genetic polymorphisms and coronary heart disease risk: a meta-analysis

Abstract

BackgroundGenetic variations in TGFB1 gene have been studied in relation to coronary heart disease (CHD) risk, but the results were inconsistent.MethodsWe performed a systematic review of published studies on the potential role of TGFB1 genetic variation in CHD risk. Articles that reported the association of TGFB1 genetic variants with CHD as primary outcome were searched via Medline and HuGE Navigator through July 2011. The reference lists from included articles were also reviewed.ResultsData were available from 4 studies involving 1777 cases and 7172 controls for rs1800468, 7 studies involving 5935 cases and 10677 controls for rs1800469, 7 studies involving 6634 cases and 9620 controls for rs1982073, 5 studies involving 5452 cases and 9999 controls for rs1800471, and 4 studies involving 5143 cases and 4229 controls for rs1800472. The pooled odds ratios (ORs) for CHD among minor T allele carriers of rs1800469, minor C allele carriers of rs1982073, and minor C allele carriers of rs1800471 versus homozygous major allele carriers was 1.14 (95% confidence interval [CI]: 1.05-1.24), 1.18 (95% CI: 1.04-1.35), and 1.16 (95% CI: 1.02-1.32), respectively. No substantial heterogeneity for ORs was detected among the included Caucasian populations for all SNPs. However, for rs1800471, the statistical significance disappeared after adjusting for potential publication bias. No significant association was found between rs1800468 and rs1800472 variants and CHD risk.ConclusionMinor allele carriers of two genetic variants (rs1800469 and rs1982073) in TGFB1 have a 15% increased risk of CHD.

TGFβ, smooth muscle cells and coronary artery disease: a review

“…Several genome-wide association studies (GWAS) have identified an association between CAD and single nucleotide polymorphisms (SNPs) in genes encoding TGFβ signalling pathway components. For example, functional polymorphisms in the promoter, signal peptide sequence and coding sequence of the TGFβ1 gene are associated with increased risk of myocardial infarction [ 64 , 65 ]) and stroke [ 66 ]; meta-analyses have also shown an association between these polymorphisms and CAD [ [67] , [68] , [69] , [70] ]. In addition, a joint analysis of two GWAS on CAD patients identified an association with an intronic SNP in the SMAD3 gene [ 71 ] which was later shown to reduce enhancer activity and attenuate Smad3 expression [ 72 , 73 ].…”

TGF-β1 Gene -509C/T Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis Involving 11,701 Subjects

“…In their meta-analysis, only seven individual studies were included. Among these included individual studies, one study by Sie deviating from the HWE was not excluded (Lu et al, 2012 ). Hence, the results from the two above meta-analysises published before were not as accurate as that deduced from the current meta-analysis.…”

“…Many other environmental factors as age, smoke, gender, obesity, dyslipidemia, diabetes mellitus, and hypertension might affect the CAD development. Since these factors were not matched in most of individual studies, it was difficult to analyze their effect on the CAD progress (Lu et al, 2012 ). Additionally, according to our knowledge it is >1000-fold confirmed association between given polymorphism and the risk of CAD.…”

Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial

“…Therefore, TGF-β1 has been implicated in the pathogenesis of autoimmune disease, carcinogenesis, and cardiovascular disease 24 . Evidence indicates that TGF-β is implicated in cardiovascular disease with significantly higher plasma levels of activated TGF-β in patients with coronary heart disease 25 . We hypothesize that memantine increased the activation of the immune response to heroin and methadone use by maintaining the plasma TGF-β1 levels.…”