<it>N-acetyltransferase 8</it>, a positional candidate for blood pressure and renal regulation: resequencing, association and <it>in silico </it>study
<p>Abstract</p> <p>Background</p> <p>Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, <...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Book |
| Published: |
BMC,
2008-04-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <p>Abstract</p> <p>Background</p> <p>Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, <it>N-acetyltransferase 8 (NAT8) </it>expressed in embryonic and adult kidney and associated with nephrotoxicity response.</p> <p>Methods/Results</p> <p>We report the first study exploring <it>NAT8 </it>as a potential candidate gene for blood pressure and kidney function. The resequencing (n = 42, random Estonian samples) identified 15 <it>NAT8 </it>polymorphisms, including 6 novel variants. The diversity of <it>NAT8 </it>5' upstream region (π/bp = 0.00320) exceeded up to 10 times the variation in the <it>NAT8 </it>genic region (π/bp = 0.00037) as well as the average variation (π/bp = 0.00040) for the promoters of 29 reference genes associated with hypertension. We suggest that a potential source for such high variation could be an active gene conversion process from <it>NAT8B </it>duplicate gene to <it>NAT8</it>. Similarly to <it>NAT8</it>, several reference genes with the most variable upstream regions have also duplicate copies. The <it>NAT8 </it>promoter SNPs were targeted with pilot quantitative association studies for blood pressure (n = 137, healthy unrelated individuals) and for the index of kidney function - estimated glomerular filtration rate (eGFR; n = 157 hypertensives with and without nephropathy). Minor alleles of these polymorphisms revealed a significant protective effect against elevated systolic BP as well as kidney failure in hypertension patients (p < 0.05; linear regression model, addictive effect).</p> <p>Conclusion</p> <p>The full resequencing and pilot association study of a novel positional candidate gene for blood pressure and renal function, human <it>N-acetyltransferase 8</it>, suggested a contribution of highly variable <it>NAT8 </it>promoter polymorphisms in determination of systolic blood pressure and eGFR. Based on <it>in silico </it>analysis, we raise the hypothesis that the alternative SNP alleles of the <it>NAT8 </it>upstream region may have differential effect on gene expression.</p> |
|---|---|
| Item Description: | 10.1186/1471-2350-9-25 1471-2350 |