- Büsst, Cara, Bloomer, Lisa, Scurrah, Katrina, Ellis, Justine, Barnes, Timothy, Charchar, Fadi, Braund, Peter, Hopkins, Paul, Samani, Nilesh, Hunt, Steven, Tomaszewski, Maciej, Harrap, Stephen
- Authors: Büsst, Cara , Bloomer, Lisa , Scurrah, Katrina , Ellis, Justine , Barnes, Timothy , Charchar, Fadi , Braund, Peter , Hopkins, Paul , Samani, Nilesh , Hunt, Steven , Tomaszewski, Maciej , Harrap, Stephen
- Date: 2011
- Type: Text , Journal article
- Relation: Hypertension Vol. 58, no. 6 (2011), p. 1073-1078
- Full Text: false
- Reviewed:
- Description: Variants in the gene encoding the y-subunit of the epithelial sodium channel (SCNN1G) are associated with both Mendelian and quantitative effects on blood pressure. Here, in 4 cohorts of 1611 white European families composed of a total of 8199 individuals, we undertook staged testing of candidate single-nucleotide polymorphisms for SCNN1G (supplemented with imputation based on data from the 1000 Genomes Project) followed by a meta-analysis in all of the families of the strongest candidate. We also examined relationships between the genotypes and relevant intermediate renal phenotypes, as well as expression of SCNN1G in human kidneys. We found that an intronic single-nucleotide polymorphism of SCNN1G (rs13331086) was significantly associated with age-, sex-, and body mass index-adjusted blood pressure in each of the 4 populations (P<0.05). In an inverse variance-weighted meta-analysis of this single-nucleotide polymorphism in all 4 of the populations, each additional minor allele copy was associated with a 1-mm Hg increase in systolic blood pressure and 0.52-mm Hg increase in diastolic blood pressure (SE=0.33, P=0.002 for systolic blood pressure; SE=0.21, P=0.011 for diastolic blood pressure). The same allele was also associated with higher 12-hour overnight urinary potassium excretion (P=0.04), consistent with increased epithelial sodium channel activity. Renal samples from hypertensive subjects showed a nonsignificant (P=0.07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination. © 2011 American Heart Association, Inc.
- Gielen, Marij, Hageman, Geja, Antoniou, Evangelia, Nordfjall, Katarina, Mangino, Massimo, Balasubramanyam, Muthuswamy, De Meyer, Tim de, Hendricks, Audrey, Giltay, Erik, Hunt, Steven, Nettleton, Jennifer, Salpea, Klelia, Diaz, Vanessa, Farzaneh-Far, Ramin, Atzmon, Gil, Harris, Sarah, Hou, Lifang, Gilley, David, Hovatta, Iiris, Kark, Jeremy, Nassar, Hisham, Kurz, David, Mather, Karen, Willeit, Peter, Zheng, Yun-Ling, Pavanello, Sofia, Demerath, Ellen, Rode, Line, Bunout, Daniel, Steptoe, Andrew, Boardman, Lisa, Marti, Amelia, Needham, Belinda, Zheng, Wei, Ramsey-Goldman, Rosalind, Pellatt, Andrew, Kaprio, Jaakko, Hofmann, Jonathan, Gieger, Christian, Paolisso, Giuseppe, Hjelmborg, Jacob, Mirabello, Lisa, Seeman, Teresa, Wong, Jason, Van Der Harst, Pim, Broer, Linda, Kronenberg, Florian, Kollerits, Barbara, Strandberg, Timo, Eisenberg, Dan, Duggan, Catherine, Verhoeven, Josine, Schaakxs, Roxanne, Zannolli, Raffaela, Dos Reis, Rosana, Charchar, Fadi, Tomaszewski, Maciej, Mons, Ute, Demuth, Ilja, Molli, Andrea, Cheng, Guo, Krasnienkov, Dmytro, D'Antono, Bianca, Kasielski, Marek, McDonnell, Barry, Ebstein, Richard, Sundquist, Kristina, Pare, Guillaume, Chong, Michael, Zeegers, Maurice
- Authors: Gielen, Marij , Hageman, Geja , Antoniou, Evangelia , Nordfjall, Katarina , Mangino, Massimo , Balasubramanyam, Muthuswamy , De Meyer, Tim de , Hendricks, Audrey , Giltay, Erik , Hunt, Steven , Nettleton, Jennifer , Salpea, Klelia , Diaz, Vanessa , Farzaneh-Far, Ramin , Atzmon, Gil , Harris, Sarah , Hou, Lifang , Gilley, David , Hovatta, Iiris , Kark, Jeremy , Nassar, Hisham , Kurz, David , Mather, Karen , Willeit, Peter , Zheng, Yun-Ling , Pavanello, Sofia , Demerath, Ellen , Rode, Line , Bunout, Daniel , Steptoe, Andrew , Boardman, Lisa , Marti, Amelia , Needham, Belinda , Zheng, Wei , Ramsey-Goldman, Rosalind , Pellatt, Andrew , Kaprio, Jaakko , Hofmann, Jonathan , Gieger, Christian , Paolisso, Giuseppe , Hjelmborg, Jacob , Mirabello, Lisa , Seeman, Teresa , Wong, Jason , Van Der Harst, Pim , Broer, Linda , Kronenberg, Florian , Kollerits, Barbara , Strandberg, Timo , Eisenberg, Dan , Duggan, Catherine , Verhoeven, Josine , Schaakxs, Roxanne , Zannolli, Raffaela , Dos Reis, Rosana , Charchar, Fadi , Tomaszewski, Maciej , Mons, Ute , Demuth, Ilja , Molli, Andrea , Cheng, Guo , Krasnienkov, Dmytro , D'Antono, Bianca , Kasielski, Marek , McDonnell, Barry , Ebstein, Richard , Sundquist, Kristina , Pare, Guillaume , Chong, Michael , Zeegers, Maurice
- Date: 2018
- Type: Text , Journal article
- Relation: American Journal of Clinical Nutrition Vol. 108, no. 3 (2018), p. 453-475
- Relation: http://purl.org/au-research/grants/nhmrc/1123472
- Full Text: false
- Reviewed:
- Description: Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
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