Exchange Scholar Program UTSW and the 1st Affiliated Hospital of SYSU
Trainee: Dihua Zhang Mentor: Orson W. Moe Khashayar Sakhaee Naim M. Maalouf
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Estrogen and phosphorus, geneJc hypercalcemia and uric acid and bone health
Center of Mineral Metabolism and Clinical Research 2
Outline
Clinical research : •  Estrogen use and serum phosphorus •  Serum uric acid and bone mineral density Combined clinical and basic research : •  Familial hypocalciuric hypercalcaemia 3
Background
•  Hyperphosphatemia is associated with vascular calcificaJon and increased cardiovascular morbidity and mortality in chronic kidney disease •  Higher serum phosphorus within the normal range is associated with increased cardiovascular morbidity and mortality in the general populaJon. •  Higher serum phosphorus and lower urine phosphorus excreJon exist in postmenopausal women. 4
Aims and Methods
•  The associaJon of estrogen use with serum phosphorus in postmenopausal women. •  ParJcipants from NHANES 2003-­‐2006 and kidney stone registry at UTSW. 5
Results: Serum P changes according to gender and age
Female
Female
Male
NHANES 2003-2006
Male
UTSW stone registry
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Results: Characteris9cs of postmenopausal women with and without estrogen use
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Results: Estrogen use and Serum P changes in postmenopausal women 8
Summary
In postmenopausal women: •  Estrogen use is associated with a decrease in serum phosphorus. •  Estrogen status may account for the gender and age difference in serum phosphorus levels. •  Estrogen use may modulate CVD risk through changes in serum phosphorus.
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Outline
Clinical research : •  Estrogen use and serum phosphorus •  Serum uric acid and bone mineral density Combined clinical and basic research : •  Familial hypercalcaemia 10
Background
•  Osteoporosis is an age-­‐related disorders. •  Prior studies found some associaJon between plasma uric acid level and bone mineral density (BMD) in postmenopausal women and older men. •  Hypothesis was proposed that higher serum uric acid is protecJve against osteoporosis.
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Aims and Methods
•  The relaJonship between serum uric acid levels and BMD in general populaJon. •  ParJcipants from NHANES 2005-­‐2006. 12
Results: Associa9on of serum uric acid with bone mineral density in women 13
Results: Associa9on of serum uric acid with bone mineral density in men 14
Summary
•  Cross-­‐secJonal data analyses did not detect associaJon between serum uric acid level and BMD in the general populaJon. •  It is premature to conclude that high serum uric acid is protecJve against osteoporosis 15
Outline
Clinical research : •  Estrogen use and serum phosphorus •  Serum uric acid and bone mineral density Combined clinical and basic research : •  Familial hypocalciuric hypercalcaemia 16
Background
•  Familial hypocalciuric hypercalcemia is a rare geneJc disease resulJng from mutaJons in the gene encoding for the calcium sensing receptor. 17
Known mutations of CaSR
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Aims and Methods
•  Three paJents presented to the Mineral Metabolism Clinic with a clinical picture compaJble with familial hypocalciuric hypercalcemia •  Genotype the CaSR •  FuncJonal studies of the CasR mutants 19
S171R
A194V
I554N
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Ca induced CaSR acJvity measured by phospho-­‐ERK1/2 formaJon 21
Dose responses of Ca-­‐induced CaSR acJvity measured by p-­‐ERK1/2 : t-­‐ERK1/2 raJo
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Summary
•  S171R, A194V in exon 4 and I554N in exon 5 are novel inacJvaJng mutaJons of the CASR gene. •  These CASR gene mutaJons causes familial hypocalciuric hypercalcemia . 23
Future work at SYSU
Clinician-Clinical investigator
Specialty-Hemodialysis
Mineral Metabolism
Analysis of Clinical Database
Basic biochemistry and molecular biology techniques
Study mineral disorders in hemodialysis pa9ents.
Set up hemodialysis pa9ents Set up enzyme assays for registry .
research purpose in HD units. For example: FGF23, Klotho
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Acknowledgements
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Orson W. Moe Khashayar Sakhaee Naim M. Maalouf Beverley Adams-­‐Huet
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Ming Chang Hu Jianning Zhang Liping Li Alexandru Bobulescu
Supported by
Sun Yat-Sun University First Affiliated Hospital-UTSouthwestern
Exchange Scholars Program
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