Table 3.
LOF Mutations Within the ATF4 Transcription Factor Involved in Control of Serine Biosynthesis Are Associated With Increased Risk of PAH
| Gene | P value | Number of cases | Number of controls | OR | Biological role |
|---|---|---|---|---|---|
| ATF4 | 0.047* | 3 (0.53%) | 498 (0.14%) | 3.78 | TF that upregulates expression of PSPH, PSAT, PHGDH and SHMT2 |
| PSPH | >0.1 | … | … | … | Serine biosynthesis |
| PSAT | >0.1 | … | … | … | |
| PHGDH | >0.1 | … | … | … | |
| SHMT2 | >0.1 | … | … | … | Conversion between glycine and serine |
This analysis used whole‐exome sequencing from 578 patients with PAH and 361 675 controls. 24 Numbers refer to the total number of PAH cases and controls who carried a LOF variant under the ptvraredmg classification. 24 LOF indicates loss‐of‐function; OR, odds ratio; PAH, pulmonary arterial hypertension; PHGDH, phosphoglycerate dehydrogenase; PSAT, phosphohydroxythreonine aminotransferase; PSPH, phosphoserine phosphatase; SHMT2, serine hydroxymethyltransferase; and TF, transcription factor.
*
Statistically significant results.