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

Journal of Biomedical Science

Hanna E Abboud¹  Anthony G Comuzzie⁴  John Blangero⁴  V Saroja Voruganti³  Farook Thameem² 

[1]South Texas Veterans Healthcare System, San Antonio 78229, TX, USA

[2]Department of Biochemistry, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait

[3]UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis 28081, NC, USA

[4]Department of Genetics, Texas Biomedical Research Institute, San Antonio 78227, TX, USA

关键词: SNPs;    Genetic variants;    SOLAR;    Mexican Americans;    NTRK2;    Glomerular filtration rate (GFR);   

Others  :  1146108
DOI  :  10.1186/s12929-015-0123-5

 received in 2014-09-03, accepted in 2015-02-26,  发布年份 2015

【 摘 要 】

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 m²) in comparison to the carriers of major allele A (98 ± 25 ml/min/1.73 m²).

Conclusion

Together, our results suggest for the first time that the genetic variants in NTRK2 may regulate eGFR.

【 授权许可】

   
2015 Thameem et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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