| 1. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 2. |
- van Es, Michael A, et al.
(författare)
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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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| 3. |
- Van Es, Michael A, et al.
(författare)
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Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 10:5-6, s. 441-447
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
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| 4. |
- van Rheenen, Wouter, et al.
(författare)
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H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:5, s. 1517.e5-1517.e7
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Tidskriftsartikel (refereegranskat)abstract
- The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival. (C) 2013 Elsevier Inc. All rights reserved.
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| 5. |
- Veldhorst, Margriet A. B., et al.
(författare)
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Dose-dependent satiating effect of whey relative to casein or soy
- 2009
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Ingår i: Physiology and Behavior. - Amsterdam : Elsevier. - 0031-9384 .- 1873-507X. ; 96:4-5, s. 675-682
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Tidskriftsartikel (refereegranskat)abstract
- Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.
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| 6. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Association between dietary protein and change in body composition among children (EYHS)
- 2009
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 28:6, s. 684-688
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Growth hormone (GH) affects body composition by a relatively reduced fat mass and increased fat free mass. The intake of protein as well as the specific amino acids arginine and lysine potently stimulate GH secretion. This study investigated associations between intakes of protein, arginine, lysine and subsequent 6-year change in body composition among 8-10-year-old children.METHODS: Data of 364 children were collected from Odense, Denmark, during 1997-1998 and 6-year later as part of the European Youth Heart Study. Body mass index among children was subdivided by fat free mass index (FFMI) and fat mass index (FMI), based on skinfold measurements. Dietary intake was estimated via 24h recall. Associations between intakes of protein as well as arginine, lysine and change in FFMI and FMI were analysed by multiple linear regressions, adjusted for social economic status, puberty stage and physical activity level.RESULTS: Among lean girls inverse associations were found between protein as well as arginine and lysine intake and change in fat mass index (beta=-1.12+/-0.56, p=0.03, beta=-1.10+/-0.53, p=0.04, beta=-1.13+/-0.51, p=0.03 respectively). Furthermore among girls with a body mass index in the 5th quintile, protein intake was associated with DeltaFFMI (p=0.04), and more specific when LYS intake was high, ARG intake was associated with DeltaFFMI (p=0.04).CONCLUSION: Among girls high protein intakes may decrease body fat gain and increase fat free mass gain, depending on the available amounts and combinations of arginine and lysine.
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| 7. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Association between intake of dietary protein and 3-year-change in body growth among normal and overweight 6-year-old boys and girls (CoSCIS)
- 2010
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Ingår i: Public Health Nutrition. - Cambridge United Kingdom : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 13:5, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Growth hormone (GH) affects linear growth and body composition, by increasing the secretion of insulin-like growth factor-I (IGF-I), muscle protein synthesis and lipolysis. The intake of protein (PROT) as well as the specific amino acids arginine (ARG) and lysine (LYS) stimulates GH/IGF-I secretion. The present paper aimed to investigate associations between PROT intake as well as intake of the specific amino acids ARG and LYS, and subsequent 3-year-change in linear growth and body composition among 6-year-old children.Design: Children's data were collected from Copenhagen (Denmark), during 2001-2002, and again 3 years later. Boys and girls were separated into normal weight and overweight, based on BMI quintiles. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated. Associations between change (Delta) in height, FMI and FFMI, respectively, and habitual PROT intake as well as ARG and LYS were analysed by multiple linear regressions, adjusted for baseline height, FMI or FFMI and energy intake, age, physical activity and socio-economic status.Setting: Eighteen schools in two suburban communities in the Copenhagen (Denmark) area participated in the study. SUBJECTS: In all, 223 children's data were collected for the present study.Results: High ARG intake was associated with linear growth (beta = 1.09 (se 0.54), P = 0.05) among girls. Furthermore, in girls, DeltaFMI had a stronger inverse association with high ARG intake, if it was combined with high LYS intake, instead of low LYS intake (P = 0.03). No associations were found in boys.Conclusion: In prepubertal girls, linear growth may be influenced by habitual ARG intake and body fat gain may be relatively prevented over time by the intake of the amino acids ARG and LYS.
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| 8. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Pharmacological and physiological growth hormone stimulation tests to predict successful GH therapy in children
- 2009
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Ingår i: Journal of Pediatric Endocrinology & Metabolism (JPEM). - : Walter de Gruyter. - 0334-018X .- 2191-0251. ; 22:8, s. 679-694
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Forskningsöversikt (refereegranskat)abstract
- Although the current use of growth hormone (GH) stimulation tests (GHSTs) is still subject to debate, the tests are widely used to diagnose GH deficiency. This literature review evaluates primarily the sensitivity, specificity and reliability of GHSTs and secondarily their convenience. Single pharmacological tests typically address only a single pathway in the complex physiological regulation of GH secretion and are therefore characterized by lower sensitivity, specificity and reliability than combined pharmacological tests or physiological tests. In spite of the high levels of sensitivity, specificity and reliability, physiological tests require considerably more effort to perform, from the physician as well as from the child. Therefore, a need for an alternative, convenient, physiological GHST still remains. Oral ingestion of dietary protein is convenient in practice and may induce more physiological stimulation of GH secretion, hence may be a promising valuable addition to the existing GHSTs in GH deficiency.
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| 9. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Effects of oral ingestion of amino acids and proteins on the somatotropic axis
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Chevy Chase, Md. : Endocrine society. - 0021-972X .- 1945-7197. ; 93:2, s. 584-590
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH is an important regulator of growth and body composition. It has been shown that GH release can be promoted by iv as well as oral administration of various amino acids (AAs), especially arginine (ARG) and lysine (LYS), which are amply present in soy protein. However, the effects of dietary protein on GH secretion are less well described. OBJECTIVE AND DESIGN: In an experiment, we compared the effects of oral ingestion of a mixture reflecting the AA composition of soy protein (AA), with oral ingestion of ARG + LYS, on GH secretion in eight healthy women (body mass index 19-25 kg/m(2); age, 18-24 yr). In a second experiment, we compared oral ingestion of hydrolyzed soy protein and complete soy protein with the AA mixture on GH secretion in eight healthy women (body mass index 19-26 kg/m(2); age, 19-36 yr). Both experiments were performed in a randomized, single-blind crossover design. GH, insulin, glucose, and plasma AA were determined every 20 min, during 3 h in the first experiment and during 5 h in the second experiment. RESULTS: Peak values of GH were higher after ingestion of the AA mixture compared with ingestion of ARG + LYS (P < 0.05). GH responses, as determined by area under the curve, did not significantly differ after ingestion of the complete soy protein, hydrolyzed soy protein, or AA mixture but were all higher than after placebo (P < 0.05). Insulin responses (area under the curve) were higher after ingestion of hydrolyzed soy protein, complete soy protein, and AA mixture, compared with placebo (P < 0.05). Glucose concentrations were unaffected. CONCLUSION: Ingestion of soy protein, either hydrolyzed or intact, as well as AAs reflecting soy protein, stimulates GH release to a similar extent.
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| 10. |
- van Vught, Anneke J. A. H., et al.
(författare)
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Somatotropic responses to soy protein alone and as part of a meal
- 2008
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Ingår i: European Journal of Endocrinology. - Oslo : Scandinavian Univ. Press. - 0804-4643 .- 1479-683X. ; 159:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal. OBJECTIVE/DESIGN: We compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19-26 kg/m(2), 19-36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min. RESULTS: GH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05). CONCLUSION: The somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.
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