TABLE 5.

Mitochondrial and clinical severity of symptoms of patients after linezolid treatment in relation to genetic data^a

Haplogroup or polymorphismb	No. of carriers vs noncarriers	% of change in carriers from the rest of the cohortc
		Mitochondrial protein synthesis	No. of clinical symptoms
Haplogroups
H	9 vs 10	26.11	−40.67
U	6 vs 13	−30.49	67
No N, N*, T	4 vs 15	9.30	3.92
Polymorphisms
12S rRNA
m.709G→A	3 vs 16	26.58	47.79
m.1189T→C	2 vs 17	5.18	−19.35
961insC	1 vs 18	−46.31	400
m.1598G→A	1 vs 18	−31.12	−100
m.980T→C	1 vs 18	NA	−18.03
m.930G→A	1 vs 18	NA	170.27
m.961T→G	1 vs 18	5.35	−100
16S rRNA
m.2706A→G	10 vs 9	−16.73	68.54
m.3197T→C	3 vs 16	−25.61	133
m.1811A→C	3 vs 16	5.18	−20
m.3010G→A*	2 vs 17	−19.23	27.12
m.1888G→A	2 vs 17	40.51	135.85
m.2850T→C	1 vs 18	40.51	70.94
m.2523C→T	1 vs 18	NA	−18.03
m.2098G→A	1 vs 18	−34.95	−18.03
m.2092C→T	1 vs 18	57.34	70.94
m.1719G→A	1 vs 18	−31.12	−100
m.1703C→T	1 vs 18	−31.12	−100
m.1700T→C	1 vs 18	1.16	−18.03

^aIn addition to the polymorphisms and mutations depicted here, all the patients presented the m.750A→G and m.1438A→G polymorphisms with respect to the mitochondrial DNA Cambridge reference sequence containing these 2 rare variations. There is evidence of increased mitochondrial protein synthesis inhibition and increased severity of clinical symptoms in patients harboring mtDNA haplogroup U, mutations in 12S rRNA, and some polymorphisms in the 16S rRNA sequence. With regard to mitochondrial 12S rRNA, such a trend was relevant only for one patient carrying a mutation consisting of a cytosine insertion in position 961 of mtDNA, but no increased toxicity was associated with any of the polymorphisms detected. In contrast, no mutations were found in mitochondrial 16S rRNA, but the presence of the m.2706A→G, m.3197T→C, or m.3010G→A polymorphism was, per se, responsible for an enhanced trend toward toxicity.

^bGenetic variants with increased mitochondrial and clinical toxicity are shown in boldface. Genetic variants with reduced mitochondrial and clinical adverse manifestations are shown in italics. *, 0.05 < P < 0.12.

^cEach result is expressed as the mean percentage of variation in mitochondrial protein synthesis or in the number of clinical symptoms after linezolid treatment with respect to the baseline for one specific genetic variant relative to the rest of the cohort (those not carrying that variant). Patients presenting multiple genetic variants were analyzed for each mutation or polymorphism. Negative values indicate reductions; positive values indicate increases. NA, not applicable.