Expressive

rs117559199 (KCNC2): Peritoneal Dialysis Solute Transfer

Key takeaways

  • This variant near ATXN7L3B and KCNC2 was flagged in a genome-wide scan of patients on peritoneal dialysis.
  • The association with peritoneal solute transfer rate is suggestive, not genome-wide significant, meaning it has not been confirmed.
  • The study covered 2,850 patients from 69 centers across six countries, and is described as the first genome-wide genetic study of any peritoneal dialysis-related trait.
  • Genetic variation overall accounts for an estimated 19% of the differences in peritoneal solute transfer rates between patients.

Key takeaways

  • This variant near ATXN7L3B and KCNC2 was flagged in a genome-wide scan of patients on peritoneal dialysis.
  • The association with peritoneal solute transfer rate is suggestive, not genome-wide significant, meaning it has not been confirmed.
  • The study covered 2,850 patients from 69 centers across six countries, and is described as the first genome-wide genetic study of any peritoneal dialysis-related trait.
  • Genetic variation overall accounts for an estimated 19% of the differences in peritoneal solute transfer rates between patients.

What the research says This variant was identified in a genome-wide association study (GWAS), an unbiased scan of the entire genome for common genetic variants linked to measurable traits, investigating peritoneal solute transfer rate (PSTR) among patients with kidney failure on peritoneal dialysis. PSTR is measured as the ratio of creatinine concentration in dialysate fluid to blood plasma after four hours (the 4-hour D/P creatinine ratio), with a mean of 0.70 in the study cohort and more than three-fold variability between patients across 2,850 participants from six countries. No variant in the study, including this one, reached conventional genome-wide significance, making all reported associations exploratory and preliminary.

Reported associations

  • Peritoneal solute transfer rate (PSTR): rs117559199, located near the ATXN7L3B and KCNC2 genes, showed a suggestive (sub-genome-wide significant) correlation with the 4-hour dialysate/plasma creatinine ratio, a standard clinical measure of how efficiently waste products cross the peritoneal membrane in patients undergoing peritoneal dialysis, in a GWAS of 2,850 patients from 69 centers in six countries.

Evidence quality The GWAS that identified this variant included 2,212 participants of European ancestry and 2,850 participants in total, drawn from 69 centers in six countries (Australia, Belgium, Canada, Sweden, United Kingdom, and United States). The study authors noted that no GWAS had previously been undertaken for any peritoneal dialysis-related phenotype, making this the first genome-wide study of PSTR. No locus reached conventional genome-wide significance (typically p < 5 x 10^-8), and the association at this locus is classified as suggestive. Heritability of PSTR was estimated at 19% using genomic-restricted maximum-likelihood analysis, which supports a broad genetic contribution to the trait but does not confirm the role of any individual variant. Replication of this specific locus in an independent cohort is not reported in this study, and the evidence should be considered preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs117559199 associated with?

rs117559199 showed a suggestive association with peritoneal solute transfer rate (PSTR), which measures how quickly waste products cross the peritoneum during dialysis. The finding comes from a single GWAS and has not yet been independently replicated.

What genes are near rs117559199?

rs117559199 is located in a region containing the ATXN7L3B and KCNC2 genes. The study that identified this variant did not characterize the specific functional role of either gene in peritoneal function.

Is rs117559199 a confirmed risk variant?

No. The association with peritoneal solute transfer rate did not reach genome-wide significance, and independent replication has not been reported. This variant should be considered a preliminary finding only.

What is peritoneal solute transfer rate?

Peritoneal solute transfer rate (PSTR) measures how efficiently the peritoneum, the membrane lining the abdominal cavity, allows waste products to pass from the blood into dialysis fluid. It is assessed with a peritoneal equilibration test and expressed as the ratio of creatinine in dialysate to plasma after four hours.

How heritable is peritoneal solute transfer rate?

A genome-wide study estimated that roughly 19% of the variation in peritoneal solute transfer rate between patients is explained by inherited genetic differences, based on genomic-restricted maximum-likelihood analysis in a cohort of 2,850 patients.