Genetic variation at <i>CYP3A</i> is associated with age at menarche and breast cancer risk: a case-control study

Johnson, Nichola,Dudbridge, Frank,Orr, Nick,Gibson, Lorna,Jones, Michael E,Schoemaker, Minouk J,Folkerd, Elizabeth J,Haynes, Ben P,Hopper, John L,Southey, Melissa C,Dite, Gillian S,Apicella, Carmel,Sc BioMed Central 2014 Breast cancer research Vol.16 No.3

<P><B>Introduction</B></P><P>We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the <I>CYP3A</I> locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.</P><P><B>Methods</B></P><P>We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.</P><P><B>Results</B></P><P>We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; <I>P</I> = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; <I>P</I> = 0.004), respectively (<I>P</I><SUB>trend</SUB> = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (<I>P</I><SUB>trend</SUB> = 0.005) but not cases (<I>P</I><SUB>trend</SUB> = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (<I>P</I><SUB>het</SUB> = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR<SUB>het</SUB> = 0.84, 95% CI 0.75, 0.94; OR<SUB>hom</SUB> = 0.81, 95% CI 0.51, 1.30; <I>P</I><SUB>trend</SUB> = 0.002) but not for those who had their menarche age ≤11 years (OR<SUB>het</SUB> = 1.06, 95% CI 0.95, 1.19, OR<SUB>hom</SUB> = 1.07, 95% CI 0.67, 1.72; <I>P</I><SUB>trend</SUB> = 0.29).</P><P><B>Conclusions</B></P><P>To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.</P>

Early Cardiac Dysfunction in Biopsy-proven Nonalcoholic Fatty Liver Disease

( Peter C. Johnson ),( Anthony A. Cochet ),( Rosco S. Gore ),( Stephen A. Harrison ),( John P. Magulick ),( James K. Aden ),( Angelo H. Paredes ) 대한소화기학회 2021 대한소화기학회지 Vol.78 No.3

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of diseases from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and has been linked to cardiovascular disease and sub-clinical cardiac remodeling. This paper presents a retrospective study of biopsy-proven NAFL and NASH to examine the differences in subclinical cardiac remodeling. Methods: Patients were recruited from an institutional repository of patients with liver-biopsy-confirmed NAFLD. Patients with a transthoracic echocardiogram (TTE) within 12 months of the liver biopsy were included. The parameters of the diastolic dysfunction were reviewed for the differences between NAFL and NASH as well as between the stages and grades of NASH. Results: Thirty-three patients were included in the study, 17 with NAFL and 16 with NASH. The NASH patients were more likely to have lower platelets, higher AST, higher ALT, and higher rates of type 2 diabetes mellitus, coronary artery disease, and hypertension than the NAFL patients. The E/e’ ratio on transthoracic echocardiogram was significantly higher in NASH compared to NAFL, advanced-stage NASH compared to early stage, and high-grade NASH compared to low-grade. The E/e’ ratio was also significantly higher in NASH than NAFL in patients without diabetes mellitus. The presence of diastolic dysfunction trended toward significance. The other markers of diastolic dysfunction were similar. Logistic regression revealed a statistical association with E/e' and NASH. Conclusions: NASH patients had evidence of a higher E/e’ ratio than NAFL, and there was a trend towards a significant diastolic dysfunction. Patients with NASH compared to NAFL should be closely monitored for signs and symptoms of cardiac dysfunction. (Korean J Gastroenterol 2021;78:161-167)

A Gene Signature Predictive for Outcome in Advanced Ovarian Cancer Identifies a Survival Factor: Microfibril-Associated Glycoprotein 2

Mok, Samuel C.,Bonome, Tomas,Vathipadiekal, Vinod,Bell, Aaron,Johnson, Michael E.,Wong, kwong-kwok,Park, Dong-Choon,Hao, Ke,Yip, Daniel K.P.,Donninger, Howard,Ozbun, Laurent,Samimi, Goli,Brady, John,R Elsevier 2009 CANCER CELL Vol.16 No.6

<P><B>Summary</B></P><P>Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors. Independent evaluation confirmed the association of a prognostic gene microfibril-associated glycoprotein 2 (<I>MAGP2</I>) with poor prognosis, whereas in vitro mechanistic analyses demonstrated its ability to prolong tumor cell survival and stimulate endothelial cell motility and survival via the α<SUB>V</SUB>β<SUB>3</SUB> integrin receptor. Increased MAGP2 expression correlated with microvessel density suggesting a proangiogenic role in vivo. Thus, MAGP2 may serve as a survival-associated target.</P>

Transitional Boundary Layers ( Intermittency Measurement )

Jaffar Madadnia,Mark W. Johnson,John C. Gibbings 대한기계학회 1998 Heat transter conference Vol.4 No.1

Intensive land-based production of red and green macroalgae for human consumption in the Pacific Northwest: an evaluation of seasonal growth, yield, nutritional composition, and contaminant levels

Bradley A. Gadberry,John Colt,Desmond Maynard,Diane C. Boratyn,Ken Webb,Ronald B. Johnson,Gary W. Saunders,Richard H. Boyer 한국조류학회I 2018 ALGAE Vol.33 No.1

Turkish towel (Chondracanthus exasperatus), Pacific dulse (Palmaria mollis, also known as Red ribbon seaweed), and sea lettuce (Ulva spp.) were cultivated in a land-based intensive culture system at the Manchester Research Station, USA from August 2013 to September 2014. Macroalgae were grown in tumble-aerated tanks, harvested bimonthly for seasonal growth calculations, and analyzed for protein, lipid, ash, and amino acid content. Growth rate of all three species exhibited a similar pattern, with the highest specific growth rates occurring during the summer months (Turkish towel: 7.8%, Pacific dulse: 8.2%, and sea lettuce: 6.2%). Growth of all three species was lowest around winter solstice; with negative growth only observed in sea lettuce. On a dry weight basis significant differences in protein content existed between the three species with highest values for sea lettuce (29.5 ± 1.4%). Lipid content varied between species (0.95-2.78%) with significantly higher lipid observed in sea lettuce (0.58-4.82%). No significant differences were detected on a seasonal basis among each species. Essential amino acids accounted for 43 ± 0.9 to 47 ± 1.2% of total amino acids with Turkish towel having the highest value. Turkish towel had a significantly higher taurine level (0.82 ± 0.27) than the other macroalgae. The levels of persistent organic pollutants and heavy metals were low. The estimated annual product of the three species ranged from 50- to 70-mt dry weight ha-1 y-1, significantly higher than conventional crops. Land-based culture of these species can produce year-round harvest, consistent product quality, and low contaminant levels.

Intensive land-based production of red and green macroalgae for human consumption in the Pacific Northwest: an evaluation of seasonal growth, yield, nutritional composition, and contaminant levels

Gadberry, Bradley A.,Colt, John,Maynard, Desmond,Boratyn, Diane C.,Webb, Ken,Johnson, Ronald B.,Saunders, Gary W.,Boyer, Richard H. The Korean Society of Phycology 2018 ALGAE Vol.33 No.1

Turkish towel (Chondracanthus exasperatus), Pacific dulse (Palmaria mollis, also known as Red ribbon seaweed), and sea lettuce (Ulva spp.) were cultivated in a land-based intensive culture system at the Manchester Research Station, USA from August 2013 to September 2014. Macroalgae were grown in tumble-aerated tanks, harvested bimonthly for seasonal growth calculations, and analyzed for protein, lipid, ash, and amino acid content. Growth rate of all three species exhibited a similar pattern, with the highest specific growth rates occurring during the summer months (Turkish towel: 7.8%, Pacific dulse: 8.2%, and sea lettuce: 6.2%). Growth of all three species was lowest around winter solstice; with negative growth only observed in sea lettuce. On a dry weight basis significant differences in protein content existed between the three species with highest values for sea lettuce ($29.5{\pm}1.4%$). Lipid content varied between species (0.95-2.78%) with significantly higher lipid observed in sea lettuce (0.58-4.82%). No significant differences were detected on a seasonal basis among each species. Essential amino acids accounted for $43{\pm}0.9$ to $47{\pm}1.2%$ of total amino acids with Turkish towel having the highest value. Turkish towel had a significantly higher taurine level ($0.82{\pm}0.27$) than the other macroalgae. The levels of persistent organic pollutants and heavy metals were low. The estimated annual product of the three species ranged from 50- to $70-mt\;dry\;weight\;ha^{-1}\;y^{-1}$, significantly higher than conventional crops. Land-based culture of these species can produce year-round harvest, consistent product quality, and low contaminant levels.

Genome-wide analysis of brassinosteroid responsive small RNAs in Arabidopsis thaliana

박소영,Jae‑Han Choi,Dong‑Ha Oh,John C. Johnson,Maheshi Dassanayake,Dong‑Hoon Jeong,Man‑Ho Oh 한국유전학회 2020 Genes & Genomics Vol.42 No.8

Background Brassinosteroids (BRs) are a class of phytohormones with important roles in regulating physiological and developmental processes. Small RNAs, including small interfering RNAs and microRNAs (miRNAs), are non-protein coding RNAs that regulate gene expression at the transcriptional and post-transcriptional levels. However, the roles of small RNAs in BR response have not been studied well. Objective In this study, we aimed to identify BR-responsive small RNA clusters and miRNAs in Arabidopsis. In addition, the effect of BR-responsive small RNAs on their transcripts and target genes were examined. Methods Small RNA libraries were constructed from control and epibrassinolide-treated seedlings expressing wild-type BRI1-Flag protein under its native promoter in the bri1-5 mutant. After sequencing the small RNA libraries, differentially expressed small RNA clusters were identified by examining the expression levels of small RNAs in 100-nt bins of the Arabidopsis genome. To identify the BR-responsive miRNAs, the expression levels of all the annotated mature miRNAs, registered in miRBase, were analyzed. Previously published RNA-seq data were utilized to monitor the BR-responsive expression patterns of differentially expressed small RNA clusters and miRNA target genes. Results In results, 38 BR-responsive small RNA clusters, including 30 down-regulated and eight up-regulated clusters, were identified. These differentially expressed small RNA clusters were from miRNA loci, transposons, protein-coding genes, pseudogenes and others. Of these, a transgene, BRI1, accumulates small RNAs, which are not found in the wild type. Small RNAs in this transgene are up-regulated by BRs while BRI1 mRNA is down-regulated by BRs. By analyzing the expression patterns of mature miRNAs, we have identified BR-repressed miR398a-5p and BR-induced miR156g. Although miR398a5p is down-regulated by BRs, its predicted targets were not responsive to BRs. However, SPL3, a target of BR-inducible miR156g, is down-regulated by BRs. Conclusion BR-responsive small RNAs and miRNAs identified in this study will provide an insight into the role of small RNAs in BR responses in plants. Especially, we suggest that miR156g/SPL3 module might play a role in BR-mediated growth and development in Arabidopsis.

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

Orr, Nick,Dudbridge, Frank,Dryden, Nicola,Maguire, Sarah,Novo, Daniela,Perrakis, Eleni,Johnson, Nichola,Ghoussaini, Maya,Hopper, John L.,Southey, Melissa C.,Apicella, Carmel,Stone, Jennifer,Schmidt, M IRL Press 2015 Human molecular genetics Vol.24 No.10

<P>We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; <I>P</I>-value = 1.58 × 10<SUP>−25</SUP>). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; <I>P</I>-value = 7.89 × 10<SUP>−09</SUP>) and rs13294895 (OR = 1.09 [1.06–1.12]; <I>P</I>-value = 2.97 × 10<SUP>−11</SUP>). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; <I>P</I>-value = 2.77 × 10<SUP>−05</SUP>). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. <I>In vitro</I> analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the <I>KLF4</I> gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.</P>