Mitochondrial DNA Nucleotide Changes in Cataract and Glaucoma Patients in Senegal

Abstract

Cataract and glaucoma are the leading causes of blindness in the world. The aim of this study was to investigate the involvement of somatic mutations of the MT-CYB gene in glaucoma and cataract cases among Senegalese patients. 38 samples including 12 controls and 26 patients (18 cataracts, 8 glaucomas) were used to study polymorphism, diversity and genetic structuration of the MT-CYB gene. DNA was isolated from whole blood samples and then the gene was genotyped by PCR-Sequencing. The study of the chromatograms and sequences obtained made it possible to detect a total of twenty-four (24) variants among which nine (9) non-synonymous mutations with seven (7) different positions. Two of them were common to both pathologies (G71A, T96C) and predicted to be non-pathogenic. The insertion, T235TA was specific for glaucoma and is known to be pathogenic. Four (4) mutations were specific to cataract (T118TC, A401AC, G402C and A408AC). T118TC and A408C are predicted pathogenic. A total of four (4) haplogroups (H, J, L and M) were found in this study. The haplogroups H and L are significantly represented in patients with cataract (H: p-value = 1.72182e-09 and L: p-value = 0.000351) and glaucoma (H: p-value = 3.333e-08 and L: p-value = 0.009398). The results also revealed a differentiation only between controls and glaucoma patients (Fst = 0.17144 and p-value = 0.0019) and between controls and glaucomatous belonging to haplogroup L (Fst = 0.47368 and p-value = 0.0156). The conclusions from this work were that contrary to cataract, MT-CYB somatic mutations are involved in the occurrence of glaucoma in Senegalese and this involvement is correlated with mitochondrial haplogroup L.

Extranuclear DNA Variations in the Susceptibility of Glaucoma

“…Moreover, a pathogenic synonymous variant G4580A ( ND2 ) in PCG[ 9 10 ] a pathogenic deletion G4821del ( ND2 ) in POAG[ 10 ] and a pathogenic insertion T15684TA in glaucoma had also been reported. [ 21 ] In addition, a NS pathogenic variant C5178A ( ND2 ) was found common in two studies on Indian and Korean population[ 8 24 ] Apart from this, pathogenic variants have also been reported in RNA regions of POAG patients viz. A1453G in 12S rRNA, A1892G and A2755G in 16S rRNA and C3254T, T4336C, T4363C, C7471T, A15909G in tRNA.…”

“…Ba et al . [ 21 ] investigated the involvement of somatic mutations of the MT-CYB gene in 8 Senegalese glaucoma patients and 12 controls. The study found a pathogenic insertion specific for glaucoma at position m. T15684TA and concluded that MT-CYB somatic mutations are involved in the occurrence of glaucoma in Senegalese.…”