title: Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India.
abstract: OBJECTIVE
  The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India.
  
  
  METHODS
  A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform.
  
  
  RESULTS
  The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology.
  
  
  CONCLUSIONS
  A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India.
authors.forename: Uma Jyothi
authors.initials: UJ
authors.lastname: Kommoju
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India.
authors.forename: Subburaj Kadarkarai
authors.initials: SK
authors.lastname: Samy
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Maruda
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India.
authors.forename: Kumuda
authors.initials: K
authors.lastname: Irgam
authors.affiliation: JP Endocrine Center, Hyderabad, India.
authors.forename: Jaya Prasad
authors.initials: JP
authors.lastname: Kotla
authors.affiliation: Department of Human Genetics, Andhra University, Visakhapatnam, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Velaga
authors.affiliation: Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India.
authors.forename: Battini Mohan
authors.initials: BM
authors.lastname: Reddy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D012359:tRNA Methyltransferases / Q000235:genetics*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D012359:tRNA Methyltransferases; C525110:CDKAL1 protein, human