Association of mitochondrial polymorphism m.709G>A with Behçet’s disease


Abstract: The involvement of nuclear genes in Behçet’s disease (BD) risk has been investigated, but the role of the mitochondrial DNA (mtDNA) has been completely neglected. Mitochondria are the main intracellular source of reactive oxygen species produced during normal aerobic metabolism via the electron transport chain and since mitochondrial dysfunction may underlie a multitude of clinical features in multifactorial and multisystemic diseases such as BD, we assessed whether mtDNA single nucleotide polymorphisms (SNPs) and haplogroups confer susceptibility to BD. A total of 615 patients and 434 controls from Iran were enrolled in this study. BD diagnosis was made according to the revised International Criteria for Behçet’s Disease1 (ICBD cases). A total of 494 patients also fulfi lled the International Study Group2 criteria for diagnosis of BD (ISG cases). We genotyped 19 mtDNA SNPs which are suffi cient for classifying our Iranian cohort into their most prevalent haplogroups: West Eurasian R0, H, V, J, T, U, K, N1, N1e’I, I, X and W haplogroups; Eastern Eurasian macrohaplogroup M, D, N (except for haplogroups N1, N1e’I, I, W and X) and R (lineages except R0, JT and UK) haplogroups; and African L haplogroup (fi gure 1).3–6 Using a panel of 89 autosomal ancestry informative markers, no evidence of population admixture was found in our cohort (data not shown). Extensive genotyping quality control checks were implemented. The associations with BD risk were assessed using Pearson’s χ2 tests and logistic regression analyses with gender as a covariate. Each haplogroup was compared with all other haplogroups pooled together. Results were considered signifi cant below the conventional level of p=0.05. Since some of the markers are in linkage disequilibrium and the haplogroup comparisons are not independent, we did not perform corrections for multiple testing and uncorrected p values are reported. The general characteristics (table 1) and the observed haplogroup frequencies (fi gure 1) in our cohort are in agreement with those previously reported in the Iranian population.7 8 In the ICBD dataset, m.709G>A (A allele in 14.5% of controls, 19.6% of ICBD cases) was signifi cantly associated with BD prior