Rs1711437

A genomic convergence approach was used to show that rs1711437 in MMP20 is correlated with creatinine clearance (uncorrected p=3.6 x 10-5, empirical p=0.01). For genomic convergence, whole transcriptional profiling was first used to identify 630 genes that either change with age in the kidney or genes belonging to pathways that are enriched for genes that change with age. From these, eQTL mapping was used to find 101 genes that contained SNPs associated with expression variation that were used in an association study for creatinine clearance. Because only 2038 candidate SNPs (including SNPs that are not eQTLs) in these 101 genes were tested, p-values less than 5 x 10-5 were considered statistically significant.

Kidney function at different ages was measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study.

In the BLSA population, the genotype of rs1711437 (a nonsynonymous SNP) explains 2.1% of the variation in creatinine clearance and in the InCHIANTI population, the genotype explains 0.9% of the variation. This association is yet to be replicated in an independent population.

rs1711437 has no discernible effect on the rate of kidney aging, as the slope for the decline in GFR (creatinine clearance) over time is not influenced by MMP20 genotype. The data from BLSA and InCHIANTI show a weak effect of MMP20 genotype on GFR in young adults/middle-aged adults, but no effect on GFR in the elderly.

It is important to note that MMP20 expression does not change with age in the human kidney (it just belongs to the extracellular matrix pathway), nor is MMP20 even expressed at detectable levels in the human kidney. In fact, MMP20 is specifically expressed in tooth enamel and catalyzes the breakdown of enamel matrix proteins.

The association between MMP20 genotype and kidney function has not been replicated in additional populations.