Mitochondrial genes regulate lipid metabolism and both are associated with the pathology of glaucoma. Here, we studied the genetic association of mitochondrial genes involved in lipid metabolic pathways with glaucoma and its ocular quantitative traits (QTs).
Methods
Polymerase chain reaction based direct sequencing followed by MITOMAP analysis was performed for NADH (MT-ND1, MT-ND2, MT-ND5 and MT-ND6); Adenosine triphosphate (ATP) synthase (MT-ATPase6) and Cytochrome B subunit (MT-CYB) genes in Primary Open angle glaucoma (POAG), closed angle glaucoma (PACG) patients (N = 50 in each group) and unrelated healthy controls (N = 150). The effect of variations on protein stability was analyzed in Dynamut2 and I-Mutant2.0 server. Linear regression analysis was performed for the association of mtDNA variations with QTs.
Results
We observed 57% of unique segregating sites in patients, that were comparatively higher in MT-ND6 gene. Six common mtSNPs were statistically significant and further associated with VCDR [(m.13469T > A (MT-ND5), m.8860A > G (MT-ATPase6), m.15326A > G (MT-CYB)]. Insilico analysis showed that the disease associated variations in MT-ND5 and MT-ND6 genes decreased protein stability and loss of hydrophobic interaction. Gene expression analysis showed a higher connectivity for MT-ND5 gene with SORT1 and TMBIM6 gene.
Conclusion
Our results showed a significantly higher mutation rate in MT-ND6, MT-CYB and NT-ND5 genes in patients and also suggested a possible association between the mtSNPs and QTs. Lack of functional studies and insufficient lipid profile data to validate the study results limits the study findings and are to be addressed further in an increased sample size.
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