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- Froguel, Philippe, et al.
(författare)
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A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far. We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (P overall = 8.1×10 -59), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23±0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P total cholesterol = 0.002 and P LDL = 0.0008). Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact. © 2012 Froguel et al.
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| 2. |
- Kirkeleit, Jorunn, et al.
(författare)
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Early life origins of lung ageing : A study of lung function decline the ECRHS and NFBC1966 cohorts
- 2020
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Ingår i: European Respiratory Journal. - : ERS Publications. - 0903-1936 .- 1399-3003. ; 56
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To determine whether early life factors associated with poor lung growth and submaximal attained lung function contribute to accelerated lung function decline later in life.Methods: Participants in the European Community Respiratory Health Survey (ECRHS) and the Northern Finland Birth Cohort 1966 (NFBC1966) with lung function measured in a first (n=10,971), second (n=7,981) and third wave (n=4,849), aged 20 – 68 years, were included. Mean annual decline in maximum forced expired volume in 1 second (FEV1) and forced vital capacity (FVC) were main outcomes. Information on early life factors was provided by standardized interviews and questionnaires. We estimated the effect of early life factors including maternal age, parental smoking, season of birth, parental asthma and respiratory infections using mixed effects models, adjusted for age, FEV1 and FVC at baseline, height, and smoking habits.Results: Decline in FEV1 was accelerated in women born of a mother with asthma (β = 2.4 ml; 95% CI 0.6-4.3) or who smoked during pregnancy (1.9; 0.2-3.6), and in men having a father with asthma (3.5; 0.2-6.9) or born by Cesarean section (7.9; 1.6-14.2). Accelerated decline in FVC was associated with paternal asthma in men (4.3; 0.1-8.5) and early menarche (<12 years) in women (2.4; 0.4-4.4). No statistically significant effect on lung function decline was found for other investigated early life factors.Conclusion: Early life risk factors contribute to an accelerated lung function decline with ageing, following sex-specific patterns. Decline in FEV1 versus FVC showed slightly different patterns.
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