AIMS/HYPOTHESIS: The association between the mitochondrial DNA 16181-16193 polycytosine variant (known as the OriB variant as it maps to the OriB origin of replication) and type 2 diabetes has not been reliably characterised, with studies reporting conflicting results. We report a systematic review of published literature in Europid populations, new data from the Norfolk Diabetes Case-Control Study and a meta-analysis to help quantify this association. METHODS: We performed a systematic review identifying all the studies of the OriB variant and type 2 diabetes in Europid populations published before January 2013. We typed the OriB variant by pyrosequencing and sequencing in the Norfolk Diabetes Case-Control Study, which comprised 5,574 type 2 diabetes cases and 6,950 population-based controls. RESULTS: Overall, the meta-analysis included eight published studies plus the current new results, with a total of 11,794 type 2 diabetes cases and 14,465 controls. In the Norfolk Diabetes Case-Control Study, the OR for type 2 diabetes for the OriB variant was 1.09 (95% CI 0.96, 1.24). In a combined analysis, the relative risk for type 2 diabetes for the OriB variant in Europid populations was 1.10 (95% CI 1.01, 1.20; p = 0.03) CONCLUSIONS/ INTERPRETATION: Results from this systematic review and meta-analysis suggest that the mitochondrial DNA OriB variant is modestly associated with an increased risk of type 2 diabetes in Europid populations, with an effect size comparable with that of recently identified variants from genome-wide association studies.
AIMS/HYPOTHESIS: The association between the mitochondrial DNA 16181-16193 polycytosine variant (known as the OriB variant as it maps to the OriB origin of replication) and type 2 diabetes has not been reliably characterised, with studies reporting conflicting results. We report a systematic review of published literature in Europid populations, new data from the Norfolk Diabetes Case-Control Study and a meta-analysis to help quantify this association. METHODS: We performed a systematic review identifying all the studies of the OriB variant and type 2 diabetes in Europid populations published before January 2013. We typed the OriB variant by pyrosequencing and sequencing in the Norfolk Diabetes Case-Control Study, which comprised 5,574 type 2 diabetes cases and 6,950 population-based controls. RESULTS: Overall, the meta-analysis included eight published studies plus the current new results, with a total of 11,794 type 2 diabetes cases and 14,465 controls. In the Norfolk Diabetes Case-Control Study, the OR for type 2 diabetes for the OriB variant was 1.09 (95% CI 0.96, 1.24). In a combined analysis, the relative risk for type 2 diabetes for the OriB variant in Europid populations was 1.10 (95% CI 1.01, 1.20; p = 0.03) CONCLUSIONS/ INTERPRETATION: Results from this systematic review and meta-analysis suggest that the mitochondrial DNA OriB variant is modestly associated with an increased risk of type 2 diabetes in Europid populations, with an effect size comparable with that of recently identified variants from genome-wide association studies.
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