1.
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.
2.
Association of XRCC3 Thr241Met polymorphism and leukemia risk: evidence from a meta-analysis.
Yan, Y, Liang, H, Li, T, Guo, S, Li, M, Qin, X, Li, S
Leukemia & lymphoma. 2014;(9):2130-4
Abstract
UNLABELLED The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphism and the risk of leukemia remains inclusive or controversial. For a better understanding of the effect of XRCC3 Thr241Met (rs861539) polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase) and the Chinese Biomedical Literature Database (CBM) up to August 2013. The association between the XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk was analyzed by means of odds ratios (ORs) and 95% confidence intervals (CI). Ultimately, seven studies with 1070 cases and 1850 controls were included in the meta-analysis. There was no association between Thr241Met polymorphism and leukemia risk in any of the five models in the overall populations (T vs. C: OR = 1.43, 95% CI = 0.95-2.13, p = 0.086; TT vs. CC: OR = 1.71, 95% CI = 0.88-3.33, p = 0.112; TC vs. CC: OR = 1.35, 95% CI = 0.96-1.91, p = 0.089; TT vs. TC/CC: OR = 1.59, 95% CI = 0.87-2.89, p = 0.132; TT/TC vs. CC: OR = 1.37, 95% CI = 0.98-1.94, p = 0.070). In subgroup analysis according to ethnicity, a significant association was found between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in Asian but not in Caucasian or mixed populations. In conclusion, the results suggest no association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the overall populations but a significant association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the Asian population. Considering the limited sample size and ethnicities included in the meta-analysis, further large-scale, well-designed studies are needed to confirm our results.