Table 3.

Coagulation, inflammation and vascular candidate genes for IVH from clinical studies

Gene name, symbol, SNP	Change in Function/Structure	Reported Environment-x-Gene Interactions
Coagulation
Factor V Leiden (F5) 1601G>A	Resistance of FV to inactivation by activated protein C; hyper-coagulability	Associated with atypical timing of IVH
Methylenetetrahydrofolate reductase (MTHFR) 677C>T; 1298A>C	Decreased conversion of homocysteine to methionine; homocysteine toxic to endothelial cells	Associated with atypical timing of IVH Interactions with maternal diet & folate Interactions with perinatal hypoxia
Prothrombin (F2) 97G>A	Elevated prothrombin; hyper-coagulability
Inflammation
Interleukin 1β (IL1) 87–511T>C 87–31C>T	Impaired activation of the HPA axis; Altered CNS inflammatory response	Environmental interaction with IL-1β-511T allele and ureaplasma urealytica colonization for PVL but not for severe IVH
Interleukin 6 (IL6) 116–121C>G	Altered CNS inflammatory response
Tumor necrosis factor (TNF) 160-31G>A	Impaired acute phase reactant
Vascular
Collagen 4A1 (COL4A1)	Altered basement membrane protein in the developing cerebrovasculature	Typical and atypical onset of parenchymal IVH
Endothelial nitric oxide synthase (eNOS) 786T>C	Decreased endogenous nitric oxide
Superoxide dismutase 3 (SOD3) rs8192287 (−416TG>C)	Impaired oxidative stress response