Highlights
- •Pre diabetes mellitus (pre-DM) was associated to ASCL1 rs9997745 and PPARGC1A rs8192678 mutations.
- •The effect of ASCL1 rs9997745 on pre-DM was modulated by obesity.
- •PPARGC1A rs8192678 was associated to pre-DM risk in subjects with obesity.
- •For PPARGC1A rs8192678 the effect was attenuated by higher cardiorespiratory values.
- •Genetic assessment may help preventing pre-DM from progressing to type two diabetes.
Abstract
Pre diabetes mellitus (pre-DM) is considered an early-reversible condition that can
progress to Type 2 diabetes mellitus (T2DM) which is the main cause of death for adult
Mexican population. Gene variants influencing fasting glucose levels may constitute
helpful tool for prevention purposes in pre-DM condition. Physically active Mexican-Mestizo
adults (n = 565) were genotyped for 6 single nucleotide polymorphisms (SNPs) (ADIPOQ rs2241766,
ACSL1 rs9997745, LIPC rs1800588, PPARA rs1800206, PPARG rs1801282 and PPARGC1A rs8192678)
related to lipid and carbohydrate metabolism. Fasting glucose was measured and values
classified as pre-DM (≥100 mg/dL) or normal fasting glucose. Logistic models were used to test associations between
pre-DM condition and SNPs, and interaction with Body Mass Index (BMI) and physical
fitness components. The A allele of ASCL1 rs9997745 conferred increased risk (OR = 3.39, p = 0.001) of pre-DM which is modulated by BMI. The A allele of the PPARGC1A rs8192678
showed significant SNP*BMI (OR = 1.10, p = 0.008) interaction effect for pre-DM risk, meaning that obese subjects showed higher
pre-DM risk but normal weight subjects showed lower risk. The effect increased with
age and was attenuated by higher cardiorespiratory values. We found that both ACSL1
rs9997745 and PPARGC1A rs8192678 are associated with pre-DM, and that BMI significantly
modified their association.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Primary Care DiabetesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Prediabetes and lifestyle modification: time to prevent a preventable disease.Perm. J. 2014; 18: 88-93
- Epidemiology of type 2 diabetes in Mexico.Arch. Med. Res. 2005; 36: 188-196
- Encuesta nacional de salud y nutrición 2006.2006
- Follow-up report on the diagnosis of diabetes mellitus.Diabetes Care. 2003; 26: 3160-3168
- Acsm’s Guidelines for Exercise Testing and Prescription.Wolters Kluwer. Lippincott Williams & Wilkins, Philadelphia2013
- Heritability of fasting glucose levels in a young genetically isolated population.Diabetologia. 2006; 49: 667-672
- New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.Nat. Genet. 2010; 42: 105-116
- A replication study of the IRS1, CAPN10, TCF7L2, and PPARG gene polymorphisms associated with type 2 diabetes in two different populations of Mexico.Ann. Hum. Genet. 2011; 75: 612-620
- Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population.Diabetes. 2012; 61: 3314-3321
- Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico city.Diabet. Metab. Res. Rev. 2010; 26: 261-–270
- Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population.Mol. Genet. Metab. 2004; 81: 122-126
- Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study.Metabolism. 2010; 59: 38-45
- Association of the ATP-binding cassette transporter A1 R230C variant with early-onset type 2 diabetes in a Mexican population.Diabetes. 2008; 57: 509-513
- Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.Nature. 2014; 506: 97-101
- Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.Diabetologia. 2011; 54: 2038-2046
- Population genetics of CAPN10 and GPR35: implications for the evolution of type 2 diabetes variants.Am. J. Hum. Genet. 2005; 76: 548-560
- Hepatic lipase (LIPC) C-514T gene polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population.Exp. Mol. Pathol. 2015; 98: 93-98
- The 482Ser of PPARGA and 12Pro of PPARG2 alleles are associated with reduction of metabolic risk factors even obesity in a Mexican-Mestizo population.BioMed Res. Int. 2015; https://doi.org/10.1155/2015/285491
- Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI.Int. J. Obes. 2010; 34: 840-845
- The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.BMC Med. Genet. 2008; 9: 1
- The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study.Diabetologia. 2012; 55: 689-693
- Neuromuscular and hormonal adaptations during strength and power training. A review.J. Sports Med. Phys. Fit. 1989; 29: 9-–26
- Genetic obesity risk and attenuation effect of physical fitness in Mexican-Mestizo population: a case-control study.Ann. Hum. Genet. 2017; https://doi.org/10.1111/ahg.12190
- A means of assessing maximal oxygen intake: correlation between field and treadmill testing.JAMA. 1968; 203: 201-204
- Diagnosis and management of diabetes: synopsis ofthe 2016 American Diabetes Association standards of medical care in diabetes synopsis of the 2016 ADA standards of medical care in diabetes.Ann. Intern. Med. 2016; 164: 542-–552
- Banting lecture 2001.Diabetes. 2002; 51: 7-18
- Genes, diet and type 2 diabetes mellitus: a review.Rev. Diabet. Stud. 2007; 4: 13-–24
- Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome.J. Lipid Res. 2010; 51: 1793-1800
- Genetic association of long-chain acyl-CoA synthetase 1 variants with fasting glucose, diabetes and subclinical atherosclerosis.J. Lipid Res. 2015; https://doi.org/10.1194/jlr.M064592
- Decreased plasma adiponectin concentrations in women with dyslipidemia.J. Clin. Endocrinol. Metab. 2002; 87: 2764-2769
- Adiponectin and development of type 2 diabetes in the Pima Indian population.Lancet. 2002; 360: 57-58
- A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women.Arterioscler. Thromb. Vasc. Biol. 1999; 19: 2701-2707
- Hepatic lipase: new insights from genetic and metabolic studies.Curr. Opin. Lipidol. 1999; 10: 259-268
- Up-regulation of PPARγ coactivator-1α as a strategy for preventing and reversing insulin resistance and obesity.Med. Hypotheses. 2005; 64: 399-407
- Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes.Diabetologia. 2006; 49: 501-505
- The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.Nat. Genet. 2000; 26: 76-80
- Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico.Proc. Natl. Acad. Sci. 2009; 106: 8611-8616
- High throughput gene expression measurement with real time PCR in a microfluidic dynamic array.PLoS One. 2008; 3e1662
- High-throughput single nucleotide polymorphism genotyping using nanofluidic dynamic arrays.BMC Genom. 2009; 10: 561
- PLINK: a tool set for whole-genome association and population-based linkage analyses.Am. J. Hum. Genet. 2007; 81: 559-575
- Generalized Linear Models.CRC Press, 1989
- Multimodel inference understanding AIC and BIC in model selection.Sociol. Methods Res. 2004; 33: 261-304
- R: A Language and Environment for Statistical Computing.R Foundation for Statistical Computing, Vienna, Austria2013 (ISBN 3-900051-07-0)
- Exercise prescription for patients with type 2 diabetes and pre-diabetes: a position statement from Exercise and Sport Science Australia.J. Sci. Med. Sport. 2012; 15: 25-31
- The international HapMap project web site.Genome Res. 2005; 15: 1592-1593
- Asian affinities and continental radiation of the four founding Native American mtDNAs.Am. J. Hum. Genet. 1993; 53: 563-590
- Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis.J. Clin. Investig. 2000; 106: 847-856
- Peroxisome proliferator-activated receptor γ coactivator 1 coactivators, energy homeostasis, and metabolism.Endocr. Rev. 2006; 27: 728-–735
- Does DNA methylation of PPARGC1A influence insulin action in first degree relatives of patients with type 2 diabetes?.PloS one. 2013; 8e58384
- Gene expression in humans with diabetes and prediabetes: what have we learned about diabetes pathophysiology?.Curr. Opin. Clin. Nutr. Metab. Care. 2004; 7: 383-390
Article info
Publication history
Published online: July 21, 2018
Accepted:
July 1,
2018
Received in revised form:
May 19,
2018
Received:
May 17,
2017
Identification
Copyright
© 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
