Mitochondrial genes in lipid metabolism pathway and susceptibility to primary open and angle closure glaucoma

BackgroundMitochondrial 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).MethodsPolymerase chain reaction based direct sequencing followed by MITOMAP analysis was performed for NADH (<i>MT-ND1, MT-ND2, MT-ND5</i> and <i>MT-ND6);</i> Adenosine triphosphate (ATP) synthase <i>(MT-ATPase6)</i> and Cytochrome B subunit <i>(MT-CYB</i>) genes in Primary Open angle glaucoma (POAG), closed angle glaucoma (PACG) patients (<i>N</i> = 50 in each group) and unrelated healthy controls (<i>N</i> = 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.ResultsWe observed 57% of unique segregating sites in patients, that were comparatively higher in <i>MT-ND6 gene</i>. Six common mtSNPs were statistically significant and further associated with VCDR [(m.13469T > A <i>(MT-ND5)</i>, m.8860A > G <i>(MT-ATPase6),</i> m.15326A > G <i>(MT-CYB)</i>]. <i>Insilico</i> analysis showed that the disease associated variations in <i>MT-ND5</i> and <i>MT-ND6</i> genes decreased protein stability and loss of hydrophobic interaction. Gene expression analysis showed a higher connectivity for <i>MT-ND5</i> gene with <i>SORT1</i> and <i>TMBIM6</i> gene.ConclusionOur results showed a significantly higher mutation rate in <i>MT</i>-<i>ND6, MT-CYB</i> and <i>NT-ND5</i> 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.