The Predisposition for Type 2 Diabetes Mellitus and Metabolic Syndrome

Abstract Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are diseases caused by the interaction of genetic and non-genetic factors. Therefore, the aim of our study was to investigate the association between six common genetic polymorphisms and T2DM and MetS in males. A total of 120 T2DM, 75 MetS, and 120 healthy controls (HC) were included in the study. ACE ID, eNOS 4a/b, ATR1 A1166C, OXTR (A>G), SOD1 +35A/C, CAT-21A/T gene polymorphisms were genotyped by PCR or PCR-RFLP techniques. T2DM was diagnosed at an earlier age compared to MetS (54 vs 55 years old, p=0.0003) and the difference was greater in carriers of the OXTR G allele (54 vs 56 years old, p=0.0002) or both OXTR G and eNOS b alleles (54 vs 56, p=0.00016). The SOD1 AA genotype (O.R.=0.11, p=0.0006) and the presence of both ACE I and OXTR1 A (O.R.=0.39, p=0.0005) alleles revealed to be protective for T2DM. SOD1 AA and AC genotypes were protective factors for triglyceride (p=0.0002 and p=0.0005, respectively) and HDL cholesterol (p=0.0002 and p=0.0004, respectively) levels in T2DM patients. ACE DD was identified more frequently in hypertensive T2DM patients (O.R.=3.77, p=0.0005) and in those who reported drinking alcohol (p=0.0001) comparing to HC and T2DM patients who did not drink alcohol, respectively. We observed that T2DM patients who reported drinking alcohol had an increased frequency of ACE DD and eNOS bb (p<0.0001), or ACE DD and OXTR G (p<0.0001) compared to non-drinkers. No gene polymorphisms were associated with MetS.

[1]  E. Lontchi-Yimagou,et al.  Geographic distribution of metabolic syndrome and its components in the general adult population: a meta-analysis of global data from 28 million individuals. , 2022, Diabetes research and clinical practice.

[2]  H. Ghazal,et al.  Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis. , 2022, Diabetes & metabolic syndrome.

[3]  B. Duncan,et al.  IDF diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 , 2021, Diabetes Research and Clinical Practice.

[4]  O. Andreassen,et al.  Oxytocin-pathway polygenic scores for severe mental disorders and metabolic phenotypes in the UK Biobank , 2021, Translational Psychiatry.

[5]  H. Milnerowicz,et al.  Concentration/activity of superoxide dismutase isozymes and the pro-/antioxidative status, in context of type 2 diabetes and selected single nucleotide polymorphisms (genes: INS, SOD1, SOD2, SOD3) - Preliminary findings. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  H. Gupta,et al.  Association of eNOS and MCP-1 Genetic Variants with Type 2 Diabetes and Diabetic Nephropathy Susceptibility: A Case–Control and Meta-Analysis Study , 2021, Biochemical Genetics.

[7]  H. Milnerowicz,et al.  Alterations in Concentration/Activity of Superoxide Dismutases in Context of Obesity and Selected Single Nucleotide Polymorphisms in Genes: SOD1, SOD2, SOD3 , 2020, International journal of molecular sciences.

[8]  X. Su,et al.  Correlation between gene polymorphism in angiotensin II type 1 receptor and type 2 diabetes mellitus complicated by hypertension in a population of Inner Mongolia , 2020, BMC Medical Genetics.

[9]  P. Chen,et al.  The OXTR Polymorphism Stratified the Correlation of Oxytocin and Glucose Homeostasis in Non-Diabetic Subjects , 2019, Diabetes, metabolic syndrome and obesity : targets and therapy.

[10]  Mahmoud H. Sawalha,et al.  Metabolic syndrome and related risk factors among adults in the northern West Bank, a cross-sectional study , 2019, International health.

[11]  Nor Azian Abdul Murad,et al.  Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Type 2 Diabetic Nephropathy in Asian Populations: An Updated Meta-analysis. , 2019, Current diabetes reviews.

[12]  G. F. Taboada,et al.  Altered superoxide dismutase-1 activity and intercellular adhesion molecule 1 (ICAM-1) levels in patients with type 2 diabetes mellitus , 2019, PloS one.

[13]  G. Adler,et al.  Oxytocin response to controlled dietary sodium and angiotensin II among healthy individuals. , 2018, American journal of physiology. Endocrinology and metabolism.

[14]  M. Bornstein,et al.  Oxytocin receptor gene polymorphisms (rs53576) and early paternal care sensitize males to distressing female vocalizations , 2018, Developmental psychobiology.

[15]  Evangelos Evangelou,et al.  Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses , 2018, PloS one.

[16]  J. A. Nogueira-Machado,et al.  Cellular death, reactive oxygen species (ROS) and diabetic complications , 2018, Cell Death & Disease.

[17]  G. Pacini,et al.  Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus , 2016, Endocrine reviews.

[18]  James Chamberlain,et al.  Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes , 2016, Annals of Internal Medicine.

[19]  Habiba S. Alsafar,et al.  Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status , 2015, Disease markers.

[20]  R. Saravani,et al.  Oxytocin Receptor Gene Polymorphisms in Patients With Diabetes , 2015 .

[21]  İ. Erol,et al.  Superoxide Dismutase and Catalase Genotypes in Pediatric Migraine Patients , 2015, Journal of child neurology.

[22]  Kimberly Matheson,et al.  Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to social exclusion. , 2015, Social cognitive and affective neuroscience.

[23]  S. Kahn,et al.  Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future , 2014, The Lancet.

[24]  Amr T. M. Saeb,et al.  ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis. , 2013, Gene.

[25]  M. Hebert-Schuster,et al.  Catalase polymorphisms and metabolic diseases , 2012, Current opinion in clinical nutrition and metabolic care.

[26]  J. Mi,et al.  The ACE insertion/deletion polymorphism and its association with metabolic syndrome. , 2012, Metabolism: clinical and experimental.

[27]  J. Behravan,et al.  Association between angiotensin II type 1 receptor gene polymorphism and metabolic syndrome in a young female Iranian population. , 2010, Archives of medical research.

[28]  Jürgen Rehm,et al.  Alcohol as a Risk Factor for Type 2 Diabetes , 2009, Diabetes Care.

[29]  P. Ismail,et al.  Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects , 2008, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[30]  E. Henriksen,et al.  Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis , 2008, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[31]  J. Škrha,et al.  Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus , 2008, BMC Medical Genetics.

[32]  Vera Regitz-Zagrosek,et al.  Gender differences in the metabolic syndrome and their role for cardiovascular disease , 2006, Clinical Research in Cardiology.

[33]  M. Haberal,et al.  Association of the Genetic Polymorphisms of the Renin-Angiotensin System and Endothelial Nitric Oxide Synthase With Chronic Renal Transplant Dysfunction , 2004, Transplantation.

[34]  S. Bealer,et al.  Angiotensin II-induced release of oxytocin: interaction with norepinephrine and role in lactation , 2003, Regulatory Peptides.

[35]  Lin Zhou,et al.  [Association of insertion/deletion polymorphism in angiotensin-converting enzyme gene with hypertensive type 2 diabetes mellitus]. , 2002, Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA.

[36]  C. Fardella,et al.  Angiotensin I-converting enzyme insertion/deletion polymorphism and adrenergic response to exercise in hypertensive patients. , 2002, Medical science monitor : international medical journal of experimental and clinical research.

[37]  W. Niu,et al.  Angiotensin converting enzyme D allele is associated with an increased risk of type 2 diabetes: evidence from a meta-analysis. , 2010, Endocrine journal.

[38]  A. Covic,et al.  Association of +35A/C (intron3/exon3) polymorphism in SOD1-gene with diabetic nephropathy in type 1 diabetes. , 2010, Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie.

[39]  S. Humphries,et al.  The D allele of the ACE I/D common gene variant is associated with Type 2 diabetes mellitus in Caucasian subjects. , 2005, Molecular genetics and metabolism.

[40]  M. Araz,et al.  Association between polymorphism of the angiotensin I converting enzyme gene and hypertension in Turkish type II diabetic patients. , 2001, Acta medica.