PMID- 26544637 OWN - NLM STAT- MEDLINE DCOM- 20170417 LR - 20221207 IS - 1827-1839 (Electronic) IS - 0392-9590 (Linking) VI - 35 IP - 4 DP - 2016 Aug TI - Association of TNF-alpha gene variations with thoracic aortic dissection risk in a Chinese Han population. PG - 418-24 AB - BACKGROUND: Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-alpha were associated with TAD. METHODS: Frequency distributions of TNF-alpha promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and -238G/A) were determined by direct sequencing. TNF-alpha plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-alpha mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification. RESULTS: We found the TNF-alpha promoter -857C/T polymorphism is associated with disease progression susceptibility in TAD patients. The CC homozygote of TAD patients had a significantly higher risk of TAD than did T allele carriers (P< 0.05). Plasma TNF-alpha concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-alpha levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF-alpha mRNA levels compared with cells carrying the T allele. CONCLUSIONS: The -857C/T polymorphism of TNF-alpha promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-alpha expression in TAD patients, and may be an independent predictive factor for TAD. FAU - DU, Xiao M AU - DU XM AD - Department of Cardiology, Cardiovascular Research Institute, the General Hospital of Shenyang Military, Shenyang, Liaoning, China - wxiaozeng@163.com. FAU - Liu, Li W AU - Liu LW FAU - DU, Zhan K AU - DU ZK FAU - Gu, Ruo X AU - Gu RX FAU - Han, Ya L AU - Han YL FAU - Wang, Xiao Z AU - Wang XZ LA - eng PT - Journal Article DEP - 20151106 PL - Italy TA - Int Angiol JT - International angiology : a journal of the International Union of Angiology JID - 8402693 RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Aortic Dissection/diagnosis/ethnology/*genetics MH - Aortic Aneurysm, Thoracic/blood/diagnosis/ethnology/*genetics MH - Asian People/genetics MH - Case-Control Studies MH - China/epidemiology MH - Disease Progression MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Male MH - Middle Aged MH - Phenotype MH - Promoter Regions, Genetic MH - RNA, Messenger/blood/genetics MH - Risk Factors MH - Tumor Necrosis Factor-alpha/blood/*genetics EDAT- 2015/11/07 06:00 MHDA- 2017/04/18 06:00 CRDT- 2015/11/07 06:00 PHST- 2015/11/07 06:00 [entrez] PHST- 2015/11/07 06:00 [pubmed] PHST- 2017/04/18 06:00 [medline] AID - R34Y9999N00A150071 [pii] PST - ppublish SO - Int Angiol. 2016 Aug;35(4):418-24. Epub 2015 Nov 6.