title: No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo-European origin.
abstract: BACKGROUND
  There has been no systematic evaluation of the association between genetic variants of type 2 receptor for TNFα (TNFR2) and type 2 diabetes, despite strong biological evidence for the role of this receptor in the pathogenesis of this complex disorder. In view of this, we performed a comprehensive association analysis of TNFRSF1B variants with type 2 diabetes in 4,200 Indo-European subjects from North India.
  
  
  METHODS
  The initial phase evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439, rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we conducted replication analysis of three associated SNPs in 2,085 subjects (1,047 type 2 diabetes patients and 1,038 control subjects).
  
  
  RESULTS
  We observed nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (P < 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), P = 0.019/Pperm = 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, P = 7.2 × 10-3/Pperm = 0.019]. We also observed suggestive association of rs496888 with plasma hsCRP levels [P = 0.042]. However, the association of rs945439, rs235249 and rs17884213 with type 2 diabetes was not replicated in the second study population. Meta-analysis of the two studies also failed to detect any association with type 2 diabetes.
  
  
  CONCLUSIONS
  Our two-stage association analysis suggests that TNFRSF1B variants are not the determinants of genetic risk of type 2 diabetes in North 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: Ganesh
authors.initials: G
authors.lastname: Chauhan
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Dwivedi
authors.forename: Himanshu
authors.initials: H
authors.lastname: Dubey
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sharma
authors.forename: Bratashree
authors.initials: B
authors.lastname: Kundu
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human