title: Evaluation of neurotrophic tyrosine receptor kinase 2 (NTRK2) as a positional candidate gene for variation in estimated glomerular filtration rate (eGFR) in Mexican American participants of San Antonio Family Heart study.
abstract: BACKGROUND
  The estimated glomerular filtration rate (eGFR) is a well-known measure of kidney function and is commonly used for the diagnosis and management of patients with chronic kidney disease. The inter-individual variation in eGFR has significant genetic component. However, the identification of underlying genetic susceptibility variants has been challenging. In an attempt to identify and characterize susceptibility genetic variant(s) we previously identified the strongest evidence for linkage of eGFR occurring on chromosome 9q21 in the Mexican American participants of San Antonio Family Heart Study (SAFHS). The objective of the present study was to examine whether the common genetic variants in Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2), a positional candidate gene on 9q21, contribute to variation in eGFR.
  
  
  RESULTS
  Twelve tagging single nucleotide polymorphisms (SNPs) across the NTRK2 gene region were selected (r2 ≥ 0.80, minor allele frequency of ≥ 0.05) from the Hapmap database. SNPs were genotyped by TaqMan assay in the 848 Mexican American subjects participated in the SAFHS. Association analysis between the genotypes and eGFR (estimated by the Modification of Diet in Renal Disease equation) were performed by measured genotype approach as implemented in the program SOLAR. Of the 12 common genetic variants examined, the rs1036915 (located in 3'UTR) and rs1187274 (located in intron-14), present in perfect linkage disequilibrium, exhibited an association (P = 0.017) with eGFR after accounting for the effects of age, sex, diabetes, diabetes duration, systolic blood pressure and blood pressure medication. The carriers of minor allele of rs1036915 (G; 38%) had increased eGFR (104 ± 25 ml/min/1.73 m(2)) in comparison to the carriers of major allele A (98 ± 25 ml/min/1.73 m(2)).
  
  
  CONCLUSIONS
  Together, our results suggest for the first time that the genetic variants in NTRK2 may regulate eGFR.
authors.affiliation: Division of Nephrology, Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA. thameem@uthscsa.edu.|Department of Biochemistry, Faculty of Medicine, Kuwait University, Safat, 13110, Kuwait. thameem@uthscsa.edu.
authors.forename: Farook
authors.initials: F
authors.lastname: Thameem
authors.affiliation: Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. saroja@unc.edu.|UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, 28081, USA. saroja@unc.edu.
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. john@txbiomedgenetics.org.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. tony@txbiomedgenetics.org.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.affiliation: Division of Nephrology, Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA. abboud@uthscsa.edu.|South Texas Veterans Healthcare System, San Antonio, TX, 78229, USA. abboud@uthscsa.edu.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
mesh_terms: D000328:Adult; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005919:Glomerular Filtration Rate; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism; D013781:Texas / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D020813:Receptor, trkB