Janna Nissen | Technical University of Denmark (DTU) (original) (raw)

Papers by Janna Nissen

Research paper thumbnail of Vitamin D status and its determinants in children and adults among families in late summer in Denmark

British Journal of Nutrition, 2014

The impact of the familial relationship on vitamin D status has not been investigated previously.... more The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (568N). Data obtained from 755 apparently healthy children (4 -17 years) and adults (18 -60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September -October, and serum 25(OH)D concentration was measured by liquid chromatography -tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5 -86·7) nmol/l (range 9 -162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations ,50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P,0·001) and positively associated with dietary vitamin D intake (P¼0·008), multivitamin use (P¼ 0·019), solarium use (P¼ 0·006), outdoor stay (P¼ 0·001), sun preference (P¼0·002) and sun vacation (P,0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations .50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults. Abbreviations: 25(OH)D, 25-hydroxyvitamin D; DEQAS, Vitamin D External Quality Assessment Scheme; IQR, interquartile range; LC -MS/MS, liquid chromatography-tandem MS; NIST, National Institute of Standards and Technology; PTH, parathyroid hormone.

Research paper thumbnail of Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D₃-fortified bread and milk during winter in Denmark

The American journal of clinical nutrition, 2015

Little is known about how the genetic variation in vitamin D modulating genes influences ultravio... more Little is known about how the genetic variation in vitamin D modulating genes influences ultraviolet (UV)B-induced 25-hydroxyvitamin D [25(OH)D] concentrations. In the Food with vitamin D (VitmaD) study, we showed that common genetic variants rs10741657 and rs10766197 in 25-hydroxylase (CYP2R1) and rs842999 and rs4588 in vitamin D binding protein (GC) predict 25(OH)D concentrations at late summer and after 6-mo consumption of cholecalciferol (vitamin D₃)-fortified bread and milk. In the current study, called the Vitamin D in genes (VitDgen) study, we analyzed associations between the increase in 25(OH)D concentrations after a given dose of artificial UVB irradiation and 25 single nucleotide polymorphisms located in or near genes involved in vitamin D synthesis, transport, activation, or degradation as previously described for the VitmaD study. Second, we aimed to determine whether the genetic variations in CYP2R1 and GC have similar effects on 25(OH)D concentrations after artificial...

Research paper thumbnail of Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults

PLoS ONE, 2014

Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are ... more Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy-Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark. Citation: Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, et al. (2014) Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults. PLoS ONE 9(2): e89907.

Research paper thumbnail of Allelic Lineages of the Ficolin Genes (FCNs) Are Passed from Ancestral to Descendant Primates

PLoS ONE, 2011

The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host ce... more The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species.

Research paper thumbnail of Vitamin D status and its determinants in children and adults among families in late summer in Denmark

British Journal of Nutrition, 2014

The impact of the familial relationship on vitamin D status has not been investigated previously.... more The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (568N). Data obtained from 755 apparently healthy children (4 -17 years) and adults (18 -60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September -October, and serum 25(OH)D concentration was measured by liquid chromatography -tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5 -86·7) nmol/l (range 9 -162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations ,50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P,0·001) and positively associated with dietary vitamin D intake (P¼0·008), multivitamin use (P¼ 0·019), solarium use (P¼ 0·006), outdoor stay (P¼ 0·001), sun preference (P¼0·002) and sun vacation (P,0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations .50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults. Abbreviations: 25(OH)D, 25-hydroxyvitamin D; DEQAS, Vitamin D External Quality Assessment Scheme; IQR, interquartile range; LC -MS/MS, liquid chromatography-tandem MS; NIST, National Institute of Standards and Technology; PTH, parathyroid hormone.

Research paper thumbnail of Vitamin D status and its determinants in children and adults among families in late summer in Denmark

British Journal of Nutrition, 2014

The impact of the familial relationship on vitamin D status has not been investigated previously.... more The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (568N). Data obtained from 755 apparently healthy children (4 -17 years) and adults (18 -60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September -October, and serum 25(OH)D concentration was measured by liquid chromatography -tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5 -86·7) nmol/l (range 9 -162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations ,50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P,0·001) and positively associated with dietary vitamin D intake (P¼0·008), multivitamin use (P¼ 0·019), solarium use (P¼ 0·006), outdoor stay (P¼ 0·001), sun preference (P¼0·002) and sun vacation (P,0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations .50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults. Abbreviations: 25(OH)D, 25-hydroxyvitamin D; DEQAS, Vitamin D External Quality Assessment Scheme; IQR, interquartile range; LC -MS/MS, liquid chromatography-tandem MS; NIST, National Institute of Standards and Technology; PTH, parathyroid hormone.

Research paper thumbnail of Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D₃-fortified bread and milk during winter in Denmark

The American journal of clinical nutrition, 2015

Little is known about how the genetic variation in vitamin D modulating genes influences ultravio... more Little is known about how the genetic variation in vitamin D modulating genes influences ultraviolet (UV)B-induced 25-hydroxyvitamin D [25(OH)D] concentrations. In the Food with vitamin D (VitmaD) study, we showed that common genetic variants rs10741657 and rs10766197 in 25-hydroxylase (CYP2R1) and rs842999 and rs4588 in vitamin D binding protein (GC) predict 25(OH)D concentrations at late summer and after 6-mo consumption of cholecalciferol (vitamin D₃)-fortified bread and milk. In the current study, called the Vitamin D in genes (VitDgen) study, we analyzed associations between the increase in 25(OH)D concentrations after a given dose of artificial UVB irradiation and 25 single nucleotide polymorphisms located in or near genes involved in vitamin D synthesis, transport, activation, or degradation as previously described for the VitmaD study. Second, we aimed to determine whether the genetic variations in CYP2R1 and GC have similar effects on 25(OH)D concentrations after artificial...

Research paper thumbnail of Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults

PLoS ONE, 2014

Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are ... more Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy-Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark. Citation: Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, et al. (2014) Common Variants in CYP2R1 and GC Genes Predict Vitamin D Concentrations in Healthy Danish Children and Adults. PLoS ONE 9(2): e89907.

Research paper thumbnail of Allelic Lineages of the Ficolin Genes (FCNs) Are Passed from Ancestral to Descendant Primates

PLoS ONE, 2011

The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host ce... more The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species.

Research paper thumbnail of Vitamin D status and its determinants in children and adults among families in late summer in Denmark

British Journal of Nutrition, 2014

The impact of the familial relationship on vitamin D status has not been investigated previously.... more The impact of the familial relationship on vitamin D status has not been investigated previously. The objective of the present cross-sectional study was to assess serum 25-hydroxyvitamin D (25(OH)D) concentration and its determinants in children and adults among families in late summer in Denmark (568N). Data obtained from 755 apparently healthy children (4 -17 years) and adults (18 -60 years) recruited as families (n 200) in the VitmaD study were analysed. Blood samples were collected in September -October, and serum 25(OH)D concentration was measured by liquid chromatography -tandem MS. Information on potential determinants was obtained using questionnaires. The geometric mean serum 25(OH)D concentration was 72·1 (interquartile range 61·5 -86·7) nmol/l (range 9 -162 nmol/l), with 9 % of the subjects having 25(OH)D concentrations ,50 nmol/l. The intra-family correlation was 0·27 in all subjects, 0·24 in the adults and 0·42 in the children. Serum 25(OH)D concentration was negatively associated with BMI (P,0·001) and positively associated with dietary vitamin D intake (P¼0·008), multivitamin use (P¼ 0·019), solarium use (P¼ 0·006), outdoor stay (P¼ 0·001), sun preference (P¼0·002) and sun vacation (P,0·001), but was not associated with lifestyle-related factors in the adults when these were assessed together with the other determinants. In conclusion, the majority of children and adults among the families had serum 25(OH)D concentrations .50 nmol/l in late summer in Denmark. Both dietary and sun-related factors were determinants of vitamin D status and the familial component was stronger for the children than for the adults. Abbreviations: 25(OH)D, 25-hydroxyvitamin D; DEQAS, Vitamin D External Quality Assessment Scheme; IQR, interquartile range; LC -MS/MS, liquid chromatography-tandem MS; NIST, National Institute of Standards and Technology; PTH, parathyroid hormone.