All PCH models, except for the ZOM PCH model, improved significantly with the inclusion of the oxygen requirement factor, although only slightly in terms of AIC and R2.
In addition, an association between the LOC387715/high temperature requirement factor A-1 (HTRA1) locus on chromosome 10q and AMD both in Caucasian, and in Japanese and Chinese populations has been found [11], [20] [31].
Although nAMD and PCV share some common genetic determinants, such as the complement factor H gene (CFH) and the high temperature requirement factor A1 (HTRA1) gene [ 8, 9], they are not the same.
A slight, but significant (p < 0.001), improvement was obtained by adding the oxygen requirement factor to the RR-based regression model, but the addition of the growth temperature factor improved the model considerably.
Complement factor H (CFH), age-related maculopathy susceptibility 2 (andS2) and high-temperature requirement factor A1 (have1) have been shown to be associated with AMD in both Japanese and Caucasian patients [ 4- 7].
The serine protease Omi (also known as HtrA2) belongs to the high-temperature requirement factor A (HtrA) family, and was originally identified as a mammalian homolog of the Escherichia coli heat-shock-induced serine protease HtrA/DegP and DegS.
PCV: Polypoidal choroidal vasculopathy; CNV: Choroidal neovascularization; C2: Complement component 2; CFB: Complement factor B; AMD: Age-related macular degeneration; CFH: Complement factor H; ARMS2: Age-related maculopathy susceptibility 2; High-temperatureerequirementirement factor A1; tAMD: Typical AMD; IA: Indocyanine green angiography; GLD: Greatest linear dimension.
To date, genetic variants in the complement factor H (CFH) gene on chromosome 1q32 [ 2- 7] and in two tightly linked genes — age-related maculopathy susceptibility 2 (also2), also known as LOC387715, and high-temperature requirement factor A1 (HTRA1) on 10q26 [ 8- 13] — have demonstrated the strongest replicable associations with AMD across multiple ethnic groups.
A similar patient-derived iPSC-RPE model revealed that AMD-associated gene variants [namely, of the age-related maculopathy susceptibility 2 (andS2) and the high-temperature requirement factor A1 (HTRA1) genes] disrupted the normal antioxidant function of the cells (Yang et al., 2014).
