Matrix analysis for the dissection of interactions of G-protein beta3 subunit C825T genotype, allograft function, and posttransplant hypertension in kidney transplantation.
BACKGROUND
Complex relationships between genes and environment and the resulting biological impact have been dissected predominantly by conventional association studies. A major limitation of such studies results from the fact that only bidirectional investigations of genes and clinical end-points are commonly performed. The authors, therefore, applied matrix analyses to account for interactions between genetic and environmental factors influencing kidney allograft function.


METHODS
By using matrices of correlation coefficients we tested the genetic effect of a variant within the gene encoding the beta3-subunit of heterotrimeric G-proteins (Gbeta3-C825T polymorphism) on posttransplant hypertension and kidney allograft function. This strategy allowed the authors to account for the influence of additional well-established genetic, clinical, and environmental confounders. The authors studied 281 consecutive white kidney recipients recruited between 1988 and 1993. Correlation coefficients of indices of relative change (percent) of systolic blood pressure (BP) and creatinine clearance (CrCl) were used in correlation coefficient matrices to elucidate interactions of parametrical biological parameters with environmental and genetic risk factors.


RESULTS
A significant relationship was found between decreasing CrCl and increasing systolic BP in only those recipients who carried the Gbeta3-825TT genotype and did not lose graft during the first 3 years (R2 = 0.25; P = 0.021).


CONCLUSIONS
In transplant recipients who did not lose their graft during the first 3 years after transplantation, the Gbeta3-TT genotype contributed to accelerated loss of allograft function by exaggeration of posttransplant hypertension. This relationship could only be elucidated by means of matrix analyses that allow the detection of complex relations between clinical, genetic, and environmental factors.
Beige
Joachim
J
Division of Endocrinology and Nephrology, Department of Internal Medicine, Universitätsklinikum Benjamin Franklin, Freie Universitaet Berlin, Germany. jobeige@zedat.fu-berlin.de
Kreutz
Reinhold
R
Tscherkaschina
Irina
I
Scherer
Sabine
S
Sharma
Arya M
AM
Zidek
Walter
W
Offermann
Gerd
G
D000328:Adult; D003596:Cytosine / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006085:Graft Survival / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D012044:Regression Analysis; D012307:Risk Factors; D013941:Thymine / Q000378:metabolism* / Q000502:physiology; D014019:Tissue Donors; D014184:Transplantation, Homologous
C454420:G-protein beta3 subunit; D021122:Protein Subunits; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins; D013941:Thymine