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Novel Association Of Estimated Glomerular Filtration Rate With NKAIN2 Gene Variants In Hispanic Children
Author(s) -
Chittoor Geetha,
Haack Karin,
Laston Sandra,
Mehta Nitesh R,
Cole Shelley A,
Comuzzie Anthony G,
Butte Nancy F,
Voruganti V. Saroja
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb410
Subject(s) - renal function , genome wide association study , medicine , genetic association , creatinine , allele , endocrinology , kidney disease , obesity , biology , genotype , genetics , gene , single nucleotide polymorphism
Background Obesity has been associated with reduced kidney function and increased chronic kidney disease risk, in both adults and children. Objective To identify genetic loci contributing to the variation in estimated glomerular filtration rate (eGFR) using genome‐wide association (GWAS) approach in 789 Hispanic children of the Viva La Familia Study (VFS). Methods We conducted a GWAS using SOLAR after accounting for familial relationships. Empirical thresholds for genome‐wide significant and suggestive associations were set at p <1 × 10 −7 , and p <1 × 10 −6 , respectively. The eGFR was estimated by the ‘Bedside Schwartz Equation’, which is specially developed for children. Results Mean± SD values of serum creatinine and eGFR were 1.79 ± 0.97 mg/dL and 39.3 ± 14.7 mL/min/1,73m 2 , respectively, and were significantly different (p <3×10 −15 ) between obese (2.06 ± 1.09; 35.64 ± 14.45) and non‐obese children (1.52 ± 0.75; 43.02 ± 13.82). eGFR, adjusted for age, age * sex, and BMI z‐scores, was significantly heritable (51%, p <1×10 −16 ). The GWAS identified rs2689886 (p <9 ×10 −8 , minor allele [G] frequency [MAF] of 0.42) of Na+/K+ Transporting ATPase Interacting 2 ( NKAIN2 located on chromosome 6) to be strongly associated with eGFR. This variant also showed suggestive evidence of association with serum creatinine. NKAIN2 is a membrane enzyme that energizes the Na‐pump and evidence suggests that it has a significant role in thermogenesis, energy balance, and weight regulation. Other NKAIN2 gene variants that showed suggestive evidence of association with eGFR include rs1973961 and rs2689887, p <5×10 −7 , MAF (A) of 0.42 and 0.48. These NKAIN2 variants were not in LD, thus signifying that a number of functional variants may exist in NKAIN2 influencing variation in eGFR. Suggestive associations with eGFR were also observed for gene variants (rs10954465, rs10279045, and rs2347709) in LOC102724947 located on chromosome 7. Conclusions Children and adolescents, particularly obese, of the VFS exhibit significantly lower eGFR. Additionally, for the first time, we have shown the association of the NKAIN2 gene with eGFR and serum creatinine in Hispanic children warranting future functional studies pertaining to this gene and renal function in pediatric cohorts. Support or Funding Information R01DK092238