Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.

Fangwen Rao; Jennifer Wessel; Gen Wen; Lian Zhang; Brinda K Rana; Brian P Kennedy; Tiffany A Greenwood; Rany M Salem; Yuqing Chen; Srikrishna Khandrika; Bruce A Hamilton; Douglas W Smith; Michael G Ziegler; Nicholas J Schork; Daniel T O'Connor; N.-H. Holstein-Rathlou

doi:10.1161/HYPERTENSIONAHA.106.081679

Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.

Fangwen Rao, Jennifer Wessel, Gen Wen, Lian Zhang, Brinda K Rana, Brian P Kennedy, Tiffany A Greenwood, Rany M Salem, Yuqing Chen, Srikrishna Khandrika, Bruce A Hamilton, Douglas W Smith, Michael G Ziegler, Nicholas J Schork, Daniel T O'Connor, N.-H. Holstein-Rathlou

Biomedicinsk Institut

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

44 Citationer (Scopus)

Abstract

Udgivelsesdato: 2007-May

Originalsprog	Engelsk
Tidsskrift	Hypertension
Vol/bind	49
Udgave nummer	5
Sider (fra-til)	1015-31
Antal sider	16
DOI	https://doi.org/10.1161/HYPERTENSIONAHA.106.081679
Status	Udgivet - 2007

Bibliografisk note

Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Catecholamines; Environment; Epistasis, Genetic; Exocytosis; Female; Haplotypes; Humans; Kidney; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic; Receptors, Dopamine D1; Signal Transduction; Sympathetic Nervous System

Adgang til dokumentet

10.1161/HYPERTENSIONAHA.106.081679

Citationsformater

Rao, F., Wessel, J., Wen, G., Zhang, L., Rana, B. K., Kennedy, B. P., Greenwood, T. A., Salem, R. M., Chen, Y., Khandrika, S., Hamilton, B. A., Smith, D. W., Ziegler, M. G., Schork, N. J., O'Connor, D. T., & Holstein-Rathlou, N-H. (2007). Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism. Hypertension, 49(5), 1015-31. https://doi.org/10.1161/HYPERTENSIONAHA.106.081679

Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism. / Rao, Fangwen; Wessel, Jennifer; Wen, Gen; Zhang, Lian; Rana, Brinda K; Kennedy, Brian P; Greenwood, Tiffany A; Salem, Rany M; Chen, Yuqing; Khandrika, Srikrishna; Hamilton, Bruce A; Smith, Douglas W; Ziegler, Michael G; Schork, Nicholas J; O'Connor, Daniel T; Holstein-Rathlou, N.-H.

I: Hypertension, Bind 49, Nr. 5, 2007, s. 1015-31.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Rao, F, Wessel, J, Wen, G, Zhang, L, Rana, BK, Kennedy, BP, Greenwood, TA, Salem, RM, Chen, Y, Khandrika, S, Hamilton, BA, Smith, DW, Ziegler, MG, Schork, NJ, O'Connor, DT & Holstein-Rathlou, N-H 2007, 'Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.', Hypertension, bind 49, nr. 5, s. 1015-31. https://doi.org/10.1161/HYPERTENSIONAHA.106.081679

Rao, Fangwen ; Wessel, Jennifer ; Wen, Gen ; Zhang, Lian ; Rana, Brinda K ; Kennedy, Brian P ; Greenwood, Tiffany A ; Salem, Rany M ; Chen, Yuqing ; Khandrika, Srikrishna ; Hamilton, Bruce A ; Smith, Douglas W ; Ziegler, Michael G ; Schork, Nicholas J ; O'Connor, Daniel T ; Holstein-Rathlou, N.-H. / Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism. I: Hypertension. 2007 ; Bind 49, Nr. 5. s. 1015-31.

@article{231c8f60ab5f11ddb5e9000ea68e967b,

title = "Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.",

abstract = "Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.",

author = "Fangwen Rao and Jennifer Wessel and Gen Wen and Lian Zhang and Rana, {Brinda K} and Kennedy, {Brian P} and Greenwood, {Tiffany A} and Salem, {Rany M} and Yuqing Chen and Srikrishna Khandrika and Hamilton, {Bruce A} and Smith, {Douglas W} and Ziegler, {Michael G} and Schork, {Nicholas J} and O'Connor, {Daniel T} and N.-H. Holstein-Rathlou",

note = "Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Catecholamines; Environment; Epistasis, Genetic; Exocytosis; Female; Haplotypes; Humans; Kidney; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic; Receptors, Dopamine D1; Signal Transduction; Sympathetic Nervous System",

year = "2007",

doi = "10.1161/HYPERTENSIONAHA.106.081679",

language = "English",

volume = "49",

pages = "1015--31",

journal = "Hypertension",

issn = "0194-911X",

publisher = "Lippincott Williams & Wilkins",

number = "5",

}

TY - JOUR

T1 - Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.

AU - Rao, Fangwen

AU - Wessel, Jennifer

AU - Wen, Gen

AU - Zhang, Lian

AU - Rana, Brinda K

AU - Kennedy, Brian P

AU - Greenwood, Tiffany A

AU - Salem, Rany M

AU - Chen, Yuqing

AU - Khandrika, Srikrishna

AU - Hamilton, Bruce A

AU - Smith, Douglas W

AU - Ziegler, Michael G

AU - Schork, Nicholas J

AU - O'Connor, Daniel T

AU - Holstein-Rathlou, N.-H.

N1 - Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Albuminuria; Catecholamines; Environment; Epistasis, Genetic; Exocytosis; Female; Haplotypes; Humans; Kidney; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic; Receptors, Dopamine D1; Signal Transduction; Sympathetic Nervous System

PY - 2007

Y1 - 2007

N2 - Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.

AB - Albumin excretion marks early glomerular injury in hypertension. This study investigated heritability of albumin excretion in twin pairs and its genetic determination by adrenergic pathway polymorphism. Genetic associations used single nucleotide polymorphisms at adrenergic pathway loci spanning catecholamine biosynthesis, storage, catabolism, receptor action, and postreceptor signal transduction. We studied 134 single nucleotide polymorphisms at 46 loci for a total of >51,000 genotypes. Albumin excretion heritability was 45.2+/-7.4% (P=2x10(-7)), and the phenotype aggregated significantly with adrenergic, renal, metabolic, and hemodynamic traits. In the adrenergic system, excretions of both norepinephrine and epinephrine correlated with albumin. In the kidney, albumin excretion correlated with glomerular and tubular traits (Na(+) and K(+) excretion; fractional excretion of Na(+) and Li(+)). Albumin excretion shared genetic determination (genetic covariance) with epinephrine excretion, and environmental determination with glomerular filtration rate and electrolyte intake/excretion. Albumin excretion associated with polymorphisms at multiple points in the adrenergic pathway: catecholamine biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention, diagnosis, and treatment.

U2 - 10.1161/HYPERTENSIONAHA.106.081679

DO - 10.1161/HYPERTENSIONAHA.106.081679

M3 - Journal article

C2 - 17353515

VL - 49

SP - 1015

EP - 1031

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -