BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males

BCL11A is a critical modulator involved in hemoglobin switching. Recent studies have established an association between BCL11A gene polymorphisms and a risk of type 2 diabetes (T2D). The aim of the present study was to assess the correlation between BCL11A DNA methylation and T2D. A total of 48 T2D cases and 48 age- and gender-matched controls were recruited to evaluate BCL11A methylation using bisulfite pyrosequencing technology. Although no significant association was observed in BCL11A methylation between T2D patients and healthy controls (P=0.322), breakdown analysis by gender identified a significant association between BCL11A methylation and T2D in males (P=0.018). Notably, there was also a significant female-specific association between the mean BCL11A DNA methylation and triglyceride (TG) concentration (r=−0.34; P=0.019). The results indicated that BCL11A methylation contributed to the risk of T2D in males. In addition, BCL11A methylation may have an effect on the development of T2D by influencing TG metabolism. Thus, gender difference may provide new information to aid the understanding of T2D pathogenesis.

[1]  J. Martín-Subero,et al.  Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. , 2013, Biochimica et biophysica acta.

[2]  L. Groop,et al.  Effects of Common Genetic Variants Associated With Type 2 Diabetes and Glycemic Traits on α- and β-Cell Function and Insulin Action in Humans , 2013, Diabetes.

[3]  J. Zierath,et al.  Epigenetic flexibility in metabolic regulation: disease cause and prevention? , 2013, Trends in cell biology.

[4]  S. Duan,et al.  Gender-dependent miR-375 promoter methylation and the risk of type 2 diabetes , 2013, Experimental and therapeutic medicine.

[5]  S. Orkin,et al.  Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A , 2013, Proceedings of the National Academy of Sciences.

[6]  R. Maitland,et al.  Severe hypertriglyceridaemia in Type 2 diabetes mellitus: beneficial effect of continuous insulin infusion. , 2013, QJM : monthly journal of the Association of Physicians.

[7]  S. Duan,et al.  Elevated PLA2G7 Gene Promoter Methylation as a Gender-Specific Marker of Aging Increases the Risk of Coronary Heart Disease in Females , 2013, PloS one.

[8]  R. Simmons.  Programming of DNA methylation in type 2 diabetes , 2013, Diabetologia.

[9]  M. Okada,et al.  Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non–small cell lung cancer , 2013, Cancer.

[10]  J. Luebke,et al.  A Mutant Prion Protein Sensitizes Neurons to Glutamate-Induced Excitotoxicity , 2013, The Journal of Neuroscience.

[11]  B. Kestenbaum,et al.  Kidney disease and increased mortality risk in type 2 diabetes. , 2013, Journal of the American Society of Nephrology : JASN.

[12]  C. Licciardello,et al.  Macrovascular complication phenotypes in type 2 diabetic patients , 2013, Cardiovascular Diabetology.

[13]  Shannon Burke,et al.  Bcl11a is essential for lymphoid development and negatively regulates p53 , 2012, The Journal of experimental medicine.

[14]  M. McCarthy,et al.  The Genetic and Epigenetic Basis of Type 2 Diabetes and Obesity , 2012, Clinical pharmacology and therapeutics.

[15]  D. Mozaffarian,et al.  Healthful Dietary Patterns and Type 2 Diabetes Mellitus Risk Among Women With a History of Gestational Diabetes Mellitus , 2012 .

[16]  D. Labie.  BCL11A contrôle l’expression de l’hémoglobine fœtale , 2012 .

[17]  P. Sfikakis,et al.  Type 2 diabetes mellitus is associated with obesity, smoking and low socioeconomic status in large and representative samples of rural, urban, and suburban adult Greek populations , 2012, Hormones.

[18]  J. Price,et al.  Gender-specific alterations in fibrin structure function in type 2 diabetes: associations with cardiometabolic and vascular markers. , 2012, The Journal of clinical endocrinology and metabolism.

[19]  K. Lillycrop,et al.  Epigenetics: are there implications for personalised nutrition? , 2012, Current opinion in clinical nutrition and metabolic care.

[20]  Jing Dai,et al.  [Association between leptin gene promoter methylation and type 2 diabetes mellitus]. , 2012, Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.

[21]  E. Gilbert,et al.  Epigenetics: The missing link to understanding β-cell dysfunction in the pathogenesis of type 2 diabetes , 2012, Epigenetics.

[22]  J. R. Pilsner,et al.  DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. , 2012, Epigenomics.

[23]  T. Zeng,et al.  Methylation status of CpG sites in the MCP-1 promoter is correlated to serum MCP-1 in Type 2 diabetes , 2012, Journal of Endocrinological Investigation.

[24]  C. Ling,et al.  Increased DNA Methylation and Decreased Expression of PDX-1 in Pancreatic Islets from Patients with Type 2 Diabetes. , 2012 .

[25]  C. Nejjari,et al.  European genetic variants associated with type 2 diabetes in North African Arabs. , 2012, Diabetes & metabolism.

[26]  J. McGavock,et al.  Success with lifestyle monotherapy in youth with new-onset type 2 diabetes. , 2012, Paediatrics & child health.

[27]  C. Hanis,et al.  Single Nucleotide Polymorphisms in JAZF1 and BCL11A gene are nominally associated with Type 2 Diabetes in African American Families from the GENNID Study , 2011, Journal of Human Genetics.

[28]  P. Franks.  Gene × Environment Interactions in Type 2 Diabetes , 2011, Current diabetes reports.

[29]  M. Panteghini,et al.  IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 °C. Part 9: Reference procedure for the measurement of catalytic concentration of alkaline phosphatase , 2011, Clinical chemistry and laboratory medicine.

[30]  H. Wanibuchi,et al.  Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis , 2011, Journal of toxicologic pathology.

[31]  J. Houwing-Duistermaat,et al.  Gene Variants in the Novel Type 2 Diabetes Loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B Affect Different Aspects of Pancreatic β-Cell Function , 2009, Diabetes.

[32]  Gonçalo R. Abecasis,et al.  Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemia , 2008, Proceedings of the National Academy of Sciences.

[33]  Mark G. Kosowski,et al.  Gender-specific care of the patient with diabetes: review and recommendations. , 2006, Gender medicine.

[34]  Mark Woodward,et al.  Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies , 2005, BMJ : British Medical Journal.

[35]  M. Panteghini,et al.  IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37°C. Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase , 2002 .

[36]  G. Velho,et al.  Fetal hemoglobin levels are related to metabolic control in diabetic subjects. , 1999, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[37]  Guo Jian,et al.  Immobilization of Glucose Oxidase and Peroxidase and Their Application in Flow‐Injection Analysis for Glucose in Serum , 1990, Annals of the New York Academy of Sciences.

[38]  Peilin Huang,et al.  Maternal protein restriction in rats leads to reduced PGC-1α expression via altered DNA methylation in skeletal muscle. , 2013, Molecular medicine reports.

[39]  E. Bonora,et al.  Triglyceride-high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus. , 2012, Metabolism: clinical and experimental.

[40]  D. Labie.  [BCL11A controls the expression of the human fetal hemoglobin]. , 2012, Medecine sciences : M/S.

[41]  Emil Ginter,et al.  Global prevalence and future of diabetes mellitus. , 2012, Advances in experimental medicine and biology.

[42]  N. Copeland,et al.  Bcl 11 a is essential for lymphoid development and negatively regulates p 53 , 2012 .

[43]  石井 真実.  Enhanced urinary bladder, liver and colon carcinogenesis in Zucker diabetic fatty rats in a multiorgan carcinogenesis bioassay : evidence for mechanisms involving activation of PI3K signaling and impairment of p53 on urinary bladder carcinogenesis , 2010 .

[44]  M. Kroll,et al.  Performance of four sources of cholesterol oxidase for serum cholesterol determination by the enzymatic endpoint method. , 2004, Clinica chimica acta; international journal of clinical chemistry.