Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.
Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6 x 10(-5), empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.
Wheeler
Heather E
HE
Department of Genetics, Stanford University Medical Center, Stanford, California, USA.
Metter
E Jeffrey
EJ
Tanaka
Toshiko
T
Absher
Devin
D
Higgins
John
J
Zahn
Jacob M
JM
Wilhelmy
Julie
J
Davis
Ronald W
RW
Singleton
Andrew
A
Myers
Richard M
RM
Ferrucci
Luigi
L
Kim
Stuart K
SK
D000375:Aging; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000502:physiology*; D053519:Matrix Metalloproteinase 20 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20