Serum lipid status in European adolescents : associations with age, gender, maturity, body mass index, percentage body fat, and fat free mass

The development of cardiovascular diseases and atherosclerosis and its relation to lipids (e.g. cholesterol, lipoproteins, and fatty acids [FA]) is well established and begins in childhood and adolescence. Beside that, an adequate lipid profile is also important for normal growth and development in youth. However, less is known about how factors associated with adolescence like age, gender, maturity, body mass index (BMI), body fat (BF), and fat free mass (FFM) are influencing lipid profiles in healthy European adolescents. Consequently, this thesis investigated the association of age, gender, maturity, BMI, BF, and FFM with the lipid profile of European adolescents within the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. More precisely, the investigated associations of the factors mentioned above with clinical lipid parameters (i.e. total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides (TG), lipoprotein(a) [Lp(a)], and the apolipoproteins (apo) A-1 and B) as well as with several lipid and lipoprotein ratios are described in chapter 4. The relation of age, gender, maturity, BMI, BF, and FFM to the FA profile is presented in chapter 5. The results of the association of age, gender, maturity, BMI, BF, and FFM with several FA ratios are provided in chapter 6. Further, in chapter 7 the relationships between selected FA and TC, HDL, LDL, TG, Lp(a), apo A-1 and B are summarized. Generally, the results were as follows: the clinical lipid parameters were higher in girls than in boys. Furthermore, almost all absolute FA values were higher in girls than in boys whereas the relative FA profile showed less clear gender differences. Triglyceride levels were positively associated with age in boys. Further, in both boys and girls some FA of the absolute FA profile and the relative FA profile were related to age. Progression in maturity was associated with lower TC and HDL levels in boys and changes in TC, LDL, and apo B levels without clear direction in girls. Additionally, maturity was associated with fluctuations in the FA profile without clear pattern in boys and girls. Body mass index was hardly associated with the lipid profile of boys. By contrast, TG levels and several lipid and lipoprotein ratios increased and HDL levels decreased with higher BMI status in girls. Body fat was mainly associated with changes in the male subjects. In boys, TG, LDL, and several lipid and lipoprotein ratios increased, whereas HDL decreased with higher body fat. The FA profile and FA ratios showed minimal associations with body fat. Fat free mass was positively associated with C20:5ω3c/C18:3ω3c ratios in boys and also associated with some FA in both sexes. In chapter 7, individual serum FA (i.e. C16:0, C18:0, C18:1ω9c, C18:2ω6c, C18:3ω3c, C20:4ω6c, C20:5ω3c, and C22:6ω3c) were associated with clinical lipid parameters (i.e. TC, HDL, LDL, TG, Lp(a), apo A-1, and apo B) using multiple linear regression models. The effect of individual FA on several lipids and lipoproteins was minimal. The highest association was found between C16:0 and C18:0 with TG levels. In boys and girls, approximately 7% and 4% of the TG level variability could be related to C16:0 and C18:0. The other clinical lipid parameters showed minor associations (R2; change=0.2%-3.5%) in both sexes.Serum-Lipidstatus in europäischen Jugendlichen – Assoziationen mit Alter, Geschlecht, Reife, Body-Mass-Index, prozentualem Körperfettanteil und Magermasse Das Auftreten von kardiovaskulären Erkrankungen und Atherosklerose steht in engem Zusammenhang mit Blutlipiden (z. Bsp. Cholesterol, Lipoproteinen, Fettsäuren [FS]), wobei erste Ausprägungen schon in früher Kindheit bzw. im Jugendalter diagnostiziert wurden. Andererseits sind adäquate Blutlipidwerte für ein normales Wachstum und eine entsprechende Entwicklung in diesem Alter von großer Bedeutung. Allerdings sind Faktoren, die die Adoleszenz beeinflussen können, wie Alter, Geschlecht, sexuelle Reife, Body-Mass-Index (BMI), prozentualer Körperfettanteil (BF) und die Magermasse (FFM), in gesunden europäischen Jugendlichen nicht hinreichend untersucht. Daher war das Ziel dieser Arbeit, den Zusammenhang zwischen Alter, Geschlecht, Reife, BMI, BF und FFM und den Blutlipiden von europäischen Jugendlichen anhand der Daten der Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Studie zu untersuchen. In Kapitel 4 der Arbeit wurden die Assoziationen zwischen den oben genannten Faktoren und den klinischen Lipidparametern Gesamtcholesterin (TC), HDL, LDL, Triglyzeriden (TG), Lipoprotein(a) [Lp(a)], den Apolipoproteinen (apo) A-1 und B sowie verschiedenen Lipidund Lipoproteinquotienten beschrieben. Weitere Schwerpunkte wurden auf die Zusammenhänge zwischen Alter, Geschlecht, Reife, BMI, BF sowie FFM und dem FS-Profil (Kapitel 5) und den FS-Quotienten (Kapitel 6) gelegt. In Kapitel 7 wurde beschrieben, inwieweit ausgewählte FS einen Zusammenhang mit den klinischen Lipidparametern zeigten. Aus der vorliegenden Arbeit lassen sich folgenden Ergebnisse zusammenfassen: Mädchen wiesen höhere Werte der klinischen Lipidparameter auf als Jungen. Dasselbe wurde für die meisten absoluten FS-Werte beobachtet. Darüber hinaus waren die FS der prozentualen Verteilung nicht eindeutig geschlechtsspezifisch erhöht. Die TG-Werte der Jungen zeigten einen positiven Zusammenhang mit dem Alter. Weiterhin waren einige FS des relativen und absoluten FS-Musters bei Jungen und Mädchen mit dem Alter assoziiert. Sinkende TC- und HDL-Werte waren bei männlichen Teilnehmern mit fortschreitender sexueller Reife zu beobachten. Im Gegensatz dazu waren bei den weiblichen Studienteilnehmern die TC-, LDL- und Apo B-Werte mit der sexuellen Reife assoziiert, wobei jedoch ein klarer Verlauf nicht zu erkennen war. Ein eindeutiges Muster konnte auch nicht in Bezug auf das FS-Profil festgestellt werden, obwohl einige FS mit dem Fortschreiten der sexuellen Reife in Verbindung gebracht werden konnten. Dies konnte sowohl für Jungen als auch für Mädchen gezeigt werden. Die Blutlipidwerte der Jungen zeigten kaum Zusammenhänge mit dem BMI. Auf der anderen Seite waren die TG-Werte der Mädchen sowie die meisten Lipid- und Lipoproteinquotienten mit steigendem BMI erhöht und das HDL erniedrigt. Der Körperfettanteil war hauptsächlich mit Blutlipiden der männlichen Teilnehmer assoziiert. Diese zeigten erhöhte TG- und LDL-Werte sowie erhöhte Lipid- und Lipoproteinquotienten mit erhöhtem BF. Zusätzlich war das HDL der Jungen mit höherem BF erniedrigt. Das FSProfil und die FS-Quotienten zeigten nur geringe Zusammenhänge zum Körperfett. Die Magermasse war positiv assoziiert mit dem C20:5ω3c/C18:3ω3c-Quotienten der Jungen. In beiden Geschlechtern zeigten einzelne FS Zusammenhänge mit der Magermasse. In Kapitel 7 wurde der Zusammenhang zwischen den FS C16:0, C18:0, C18:1ω9c, C18:2ω6c, C18:3ω3c, C20:4ω6c, C20:5ω3c sowie C22:6ω3c und TC, HDL, LDL, TG, Lp(a), apo A-1 und B mittels multipler, linearer Regressionsanalysen untersucht. Es zeigte sich jedoch, dass der Zusammenhang zwischen den Parametern minimal war. Lediglich die FS C16:0 und C18:0 zeigten einen wesentlichen Zusammenhang mit den TG-Werten. In Jungen und Mädchen war die Variabilität der TG-Werte zu 7% bzw. 4% durch diese FS zu erklären. Die restlichen Parameter waren mit den FS in Größenordnungen von 0.2%-3.5% assoziiert

Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults

CONTEXT: Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans. OBJECTIVE: The aim of the study was to examine the association between ANGPTL3 and ANGPTL4 genetic polymorphisms and metabolic phenotypes in adolescent and adult samples. DESIGN AND PARTICIPANTS: Two independent population-based studies, one composed of 1144 adolescents (mean age, 14.8 +/- 1.4 yr) from nine European countries (the HELENA study) and the other composed of 1155 adults (age range, 35-65 yr) from Northern France (the MONICA Lille study), were genotyped for one ANGPTL3 polymorphism and four ANGPTL4 polymorphisms. RESULTS: The ANGPTL3 rs11207997 polymorphism (minor allele frequency, 0.32) was associated with lower plasma HDL-cholesterol and apolipoprotein A-I levels in both adolescents (P = 0.0004, P = 0.00006, respectively) and adults (P = 0.03, P = 0.02, respectively). The ANGPTL4 rs4076317 polymorphism (minor allele frequency, 0.29) was associated with a higher percentage of body fat (P = 0.02) in adolescents and a higher waist-to-hip ratio (in interaction with the peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism) in adults (P = 0.0004). CONCLUSION: The present study underlines the role of ANGPTL3 in HDL-cholesterol metabolism as early as in adolescence. Our data also suggest possible associations between ANGPTL4 polymorphisms and body fat, but these findings require replication

FADS1 genetic variability interacts with dietary α-linolenic acid intake to affect serum non-HDL-cholesterol concentrations in European adolescents

Two rate-limiting enzymes in PUFA biosynthesis, Delta 5- and Delta 6-desaturases, are encoded by the FADS1 and FADS2 genes, respectively. Genetic variants in the FADS1-FADS2 gene cluster are associated with changes in plasma concentrations of PUFA, HDL- and LDL-cholesterol, and TG. However, little is known about whether dietary PUFA intake modulates these associations, especially in adolescents. We assessed whether dietary linoleic acid (LA) or a-linolenic acid (ALA) modulate the association between the FADS1 rs174546 polymorphism and concentrations of PUFA, other lipids, and lipoproteins in adolescents. Dietary intakes of LA and ALA, FADS1 rs174546 genotypes, PUFA levels in serum phospholipids, and serum concentrations of TG, cholesterol, and lipoproteins were determined in 573 European adolescents from the HELENA study. The sample was stratified according to the median dietary L4 (9.4 g/d) and ALA (1.4 g/d) intakes. The associations between FADS1 rs174546 and concentrations of PUFA, TG, cholesterol, and lipoproteins were not affected by dietary LA intake (all P-interaction > 0.05). Similarly, the association between the FADS1 rs174546 polymorphism and serum phospholipid concentrations of ALA or EPA was not modified by dietary ALA intake (all P-interaction > 0.05). In contrast, the rs174546 minor allele was associated with lower total cholesterol concentrations (P = 0.01 under the dominant model) and non-HDL-cholesterol concentrations (P = 0.02 under the dominant model) in the high-ALA-intake group but not in the low-ALA-intake group (P-interaction = 0.01). These results suggest that dietary ALA intake modulates the association between FADS1 rs174546 and serum total and non-HDL-cholesterol concentrations at a young age

Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios[S]

Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents