Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth
NATURE COMMUNICATIONS
Authors: Helgeland, Oyvind; Vaudel, Marc; Juliusson, Petur B.; Holmen, Oddgeir Lingaas; Juodakis, Julius; Bacelis, Jonas; Jacobsson, Bo; Lindekleiv, Haakon; Hveem, Kristian; Lie, Rolv Terje; Knudsen, Gun Peggy; Stoltenberg, Camilla; Magnus, Per; Sagen, Jorn V.; Molven, Anders; Johansson, Stefan; Njolstad, Pal Rasmus
Abstract
Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6-12 months (rs2767486, P-6m = 2.0 x 10(-21), beta(6m) = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P-1.5y = 1.3 x 10(-8), beta(1.5y) = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.
Screening of Antiviral Components of Ma Huang Tang and Investigation on the Ephedra Alkaloids Efficacy on Influenza Virus Type A
FRONTIERS IN PHARMACOLOGY
Authors: Wei, Wenyang; Du, Haixia; Shao, Chongyu; Zhou, Huifen; Lu, Yiyu; Yu, Li; Wan, Haitong; He, Yu
Abstract
Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro, and the inhibitory effect at 24 h after the treatment was more obvious than that at 48 h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-alpha level and the up-regulation of IFN-beta level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1 beta in serum, inhibited the mRNA expression levels of TNF-alpha, TLR3, TLR4, TLR7, MyD88, NF-kappa B p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-kappa B p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-gamma. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.