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Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.
Parmar, P, Lowry, E, Cugliari, G, Suderman, M, Wilson, R, Karhunen, V, Andrew, T, Wiklund, P, Wielscher, M, Guarrera, S, et al
EBioMedicine. 2018;:206-216
Abstract
BACKGROUND DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). FINDINGS Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10-7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10-8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. INTERPRETATION Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. FUND European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer.
Xiong, T, Yang, J, Wang, H, Wu, F, Liu, Y, Xu, R, Lv, Z, Xue, P, Cao, W, Zhang, Y
Molecular biology reports. 2014;(4):2629-34
Abstract
The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case-control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95-1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02-1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case-control studies are needed to validate our results.
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Association between X-ray repair cross-complementing group 1 Arg194Trp polymorphism and colorectal cancer risk.
Mao, D, Zhang, Y, Lu, H, Fu, X
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013;(5):2529-38
Abstract
The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a substitution of Arg to Gln at position 194, has been implicated in the development of colorectal cancer (CRC) in a number of case-control studies with contradictory and inconclusive findings. The current meta-analysis of all currently available publications was conducted to assess the gene susceptibility to CRC and improve our understanding of the CRC pathogenesis. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated by use of fixed-effects model or random-effects model when appropriate. A total of 15 eligible case-control studies with 4,501 cases and 8,038 controls were retrieved after a comprehensive search of the PubMed, Embase, Web of science, and Chinese Biomedicine (CBM) databases up to December 2012. The overall meta-analysis identified a positive but not statistically significant association between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast models (ORTrp vs. Arg = 1.07, 95 % CI 0.90-1.26, P OR = 0.441; ORTrpTrp vs. ArgArg = 1.28, 95 % CI 0.91-1.81, P OR = 0.163; ORArgTrp vs. ArgArg = 1.00, 95 % CI 0.85-1.19, P OR = 0.956; ORArgTrp + TrpTrp vs. ArgArg = 1.06, 95 % CI 0.90-1.24, P OR = 0.502; ORTrpTrp vs. ArgArg + ArgTrp = 1.11, 95 % CI 0.91-1.34, P OR = 0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to CRC, although lack statistical evidence (ORTrpTrp vs. ArgArg = 2.69, 95 % CI 0.97-7.49, P OR = 0.058; ORTrpTrp vs. ArgArg + ArgTrp = 2.77, 95 % CI 0.99-7.72, P OR = 0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated with an increased risk of colon cancer. The present meta-analysis suggests that the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon cancer. However, the precise genetic association needs to be further estimated in future studies.
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[The DNA binding activity of nuclear factor-ΚB in patients with severe pneumonia and the intervention effects of Xuebijing injection].
Gong, BL, Zhang, Y, Xu, QX, Chen, YQ
Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue. 2010;(9):543-6
Abstract
OBJECTIVE To investigate the role of nuclear factor-ΚB (NF-ΚB) in severe pneumonia and observe the effects of Xuebijing injection in its treatment. METHODS Thirty hospitalized patients with severe pneumonia were divided into the routine therapy group (n=14) and Xuebijing therapy group (n=16) in whom with Xuebijing injection 100 ml was given once daily for 7 days besides routine therapies, according to the random numeral. The DNA binding activity of NF-ΚB in human monocytes was detected before and 3 days and 7 days after administration, the contents of tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were determined, and the changes in coagulatory and fibrinolytic parameters were assayed at the same time. Acute physiology and chronic health evaluationII (APACHEII) score was also recorded. Ten healthy volunteers served as the healthy control group. RESULTS The DNA binding activities of NF-ΚB, the contents of TNF-α, PCT, CRP, fibrinogen (Fib), D-dimer in hospitalized subjects with severe pneumonia were higher before treatment than those in healthy control group, while the prothrombin time (PT), thrombin time (TT) were significantly lower (P<0.05 or P<0.01). Compared with the routine therapy group, the DNA binding activity of NF-ΚB (grey level) at the 7 days (66.60±36.23 vs. 79.90±39.11) was notably decreased in Xuebijing therapy group; the levels of TNF-α (ng/L, 25.81±11.67 vs. 33.78±13.36), PCT (μg/L, 1.91±1.09 vs. 2.96±1.80), CRP (mg/L, 20.01±7.21 vs. 26.59±10.66), Fib (g/L, 4.02±1.26 vs. 5.09±1.43), D-dimer (mg/L, 0.24±0.06 vs. 0.31±0.11) were significantly lower in Xuebijing therapy group, and APACHEII score (15.81±3.47 vs. 17.93±3.05) was obviously lowered (all P<0.05). There was statistical difference of the TT (s) between two groups at 3 days (15.68±1.89 vs. 14.65±1.33,P<0.05). There was a significant positive correlation between NF-ΚB DNA binding activity and the levels of TNF-α (r(1)=0.373, r(2)=0.362, r(3)=0.419), PCT (r (1)=0.800, r(2)=0.716, r(3)=0.920) or CRP (r(1)=0.368, r(2)=0.441, r(3)=0.366, all P<0.05) before and 3 days and 7 days after the treatment. CONCLUSION NF-ΚB activation and coagulopathy were observed in patients with severe pneumonia, and NF-ΚB was involved in the process of inflammatory response. Inflammatory response was partly alleviated by Xuebijing injection. These effects of Xuebijing injection may be mediated by inhibition of the activation of NF-ΚB and its anticoagulation property.