ArticlePloS one2011
The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.Human molecular genetics · 2015Pooled it
- Rare Presentation of Heterozygous PCSK1 Deficiency in an Adolescent Male.Case reports in pediatrics · 2026Article
- Association ofGenes · 2023Article
- Reduced Stability and pH-Dependent Activity of a Common Obesity-Linked PCSK1 Polymorphism, N221D.Endocrinology · 2019Article
- Endoplasmic reticulum-associated degradation of the mouse PC1/3-N222D hypomorph and human PCSK1 mutations contributes to obesity.International journal of obesity (2005) · 2016Article
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph.Endocrinology · 2014Article
- Defective transport of the obesity mutant PC1/3 N222D contributes to loss of function.Endocrinology · 2014Article
- Association of genetic variants of the incretin-related genes with quantitative traits and occurrence of type 2 diabetes in Japanese.Molecular genetics and metabolism reports · 2014Article
- Article
- Genetics of the first seven proprotein convertase enzymes in health and disease.Current genomics · 2013Article
- Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.Diabetes · 2013Article
- Allelic clustering and ancestry-dependent frequencies of rs6232, rs6234, and rs6235 PCSK1 SNPs in a Northern Ontario population sample.Journal of community genetics · 2012Article
- Developmental origins of genotype-phenotype correlations in chronic diseases of old age.Aging and disease · 2012Article
- PCSK1 rs6232 is associated with childhood and adult class III obesity in the Mexican population.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe aimed to evaluate the effects of the G-allele of rs6232 and the C-allele of rs6235 within PCSK1 on measures of body fat and glucose homeostasis in Danish individuals and to assess interactions of genotypes with age, sex and glucose tolerance status. Data were included in meta-analyses of additional Europeans. METHODOLOGY/PRINCIPAL
findingsRs6232 and rs6235 were genotyped in 6,164 Danes from the Inter99 study of middle-aged people. Results from these analyses were combined with previously published studies in meta-analyses of a total of 27,786 individuals. The impact of the variants was also investigated in a subset of 62 glucose-tolerant men during a meal challenge including measures of serum incretins. In men we found an effect on body composition in sex-stratified analyses where the rs6235 C-allele conferred an increased waist circumference of 0.8 cm per allele (0.2-1.5, p = 0.008) and increased waist-to-hip ratio of 0.004 (0.0005-0.008, p = 0.027). In the meta-analyses where men and women were combined, the rs6232 G-allele associated with increased waist-to-hip ratio (p = 0.02) and the rs6235 C-allele associated with increased waist circumference (p = 0.01). Furthermore, the rs6235 C-allele was associated nominally with a 0.6% (0.1-1%, p = 0.01) reduction in fasting glucose, it interacted with glucose tolerance status for traits related to glucose metabolism and analysis among individuals having abnormal glucose tolerance revealed a 5% (-0.7-9%, p = 0.02) elevated level of acute insulin response for this variant. Finally, we found that the rs6232 G-allele associated with higher levels of GLP-1, GLP-2 and glucagon and that the rs6235 C-allele associated with higher levels of GIP and glucagon during a meal-test. CONCLUSIONS/SIGNIFICANCE: PCSK1 rs6232 G-allele and rs6235 C-allele have an effect on body composition which may be modified by sex, whereas the effect of rs6235 C-allele on fasting and stimulated circulating plasma glucose and hormone levels may be influenced by glucose tolerance status.
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