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Background   Zinc finger and BTB domain-containing protein 12  ( ZBTB12 ) is a predicted transcription factor with potential role in hematopoietic development. Recent evidence linked low methylation level of  ZBTB12  exon1 to myocardial infarction (MI) risk. However, the role of  ZBTB12  in the pathogenesis of MI and cardiovascular disease in general is not yet clarified. We investigated the relation between  ZBTB12  methylation and several blood parameters related to cardio-cerebrovascular risk in an Italian family-based cohort.    Results   ZBTB12  methylation was analyzed on white blood cells from the Moli-family cohort using the Sequenom EpiTYPER MassARRAY (Agena). A total of 13 CpG Sequenom units were analyzed in the small CpG island located in the only translated  ZBTB12  exon. Principal component analysis (PCA) was performed to identify groups of CpG units with similar methylation estimates. Linear mixed effect regressions showed a positive association between methylation of  ZBTB12  Factor 2 (including CpG units 8, 9–10, 16, 21) and TNF-ɑ stimulated procoagulant activity, a measure of procoagulant and inflammatory potential of blood cells. In addition, we also found a negative association between methylation of  ZBTB12  Factor 1 (mainly characterized by CpG units 1, 3–4, 5, 11, and 26) and white blood cell and granulocyte counts. An in silico prediction analysis identified granulopoiesis- and hematopoiesis-specific transcription factors to potentially bind DNA sequences encompassing CpG1, CpG3–4, and CpG11.    Conclusions   ZBTB12  hypomethylation is linked to shorter TNF-ɑ stimulated whole blood coagulation time and increased WBC and granulocyte counts, further elucidating the possible link between  ZBTB12  methylation and cardiovascular disease risk.    Electronic supplementary material  The online version of this article (10.1186/s13148-019-0665-6) contains supplementary material, which is available to authorized users.

ZBTB12 DNA methylation is associated with coagulation- and inflammation-related blood cell parameters: findings from the Moli-family cohort