title: Common variants of SLAMF1 and ITLN1 on 1q21 are associated with type 2 diabetes in Indian population.
abstract: Though multiple studies link chromosomal regions 1q21-q23 and 20q13 with type 2 diabetes, fine mapping of these regions is yet to confirm gene(s) explaining the linkages. These candidate regions remain unexplored in Indians, which is a high-risk population for type 2 diabetes. Hypothesizing regulatory regions to have a more important role in complex disorders, we examined association of 207 common variants in proximal promoter and untranslated regions of genes on 1q21-23 and 20q13 with type 2 diabetes in 2115 North Indians. Further, top signals were replicated in an independent group of 2085 North Indians. Variants-rs11265455-SLAMF1 (odds ratios (OR)=1.32, P=1.1 × 10(-3)), rs1062827-F11R (OR=1.36, P=1.7 × 10(-3)) and rs12565932-F11R (OR=1.35, P=1.8 × 10(-3)) were top signals for association with type 2 diabetes whereas rs1333062-ITLN1 (OR=1.28, P=3.4 × 10(-3)) showed strongest association in body mass index-stratified analysis. Replication of these four variants confirmed associations of rs11265455-SLAMF1 (OR=1.27, P=9.1 × 10(-3)) and rs1333062-ITLN1 (OR=1.25, P=1.1 × 10(-3)) with type 2 diabetes. Meta-analysis further corroborated the association of rs11265455-SLAMF1 (OR random effect=1.29, P random effect=3.9 × 10(-5)) and rs1333062-ITLN1 (OR random effect=1.19, P random effect=1.8 × 10(-4)). In conclusion, the study demonstrates that variants of SLAMF1 and ITLN1, both implicated in inflammation, are associated with type 2 diabetes in Indians.
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rubina
authors.initials: R
authors.lastname: Tabassum
authors.forename: Anubha
authors.initials: A
authors.lastname: Mahajan
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Dwivedi
authors.forename: Ganesh
authors.initials: G
authors.lastname: Chauhan
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Spurgeon
authors.forename: M V Kranthi
authors.initials: MV
authors.lastname: Kumar
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: S V
authors.initials: SV
authors.lastname: Madhu
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Mathur
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015992:Body Mass Index; D002878:Chromosomes, Human, Pair 1; D002890:Chromosomes, Human, Pair 20; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D037102:Lectins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D044465:White People / Q000235:genetics
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1