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Sex‐Specific Effects Of NPHP1 And SLC9A2 SNPs On Systemic Water Balance In American Indians
Author(s) -
Voruganti V Saroja,
Haack Karin,
Laston Sandra,
Goring Harald,
Best Lyle,
Howard Barbara,
MacCluer Jean,
Umans Jason,
Cole Shelley,
Cohen David
Publication year - 2015
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.29.1_supplement.748.6
Subject(s) - single nucleotide polymorphism , snp , genetics , heritability , biology , genotype , genetic association , allele , subfamily , solute carrier family , gene , transporter
Serum sodium (SNa) concentration, when doubled, provides a clinically‐useful approximation of osmolality, reflecting body water balance. Previously, we reported significant heritability of SNa in American Indian families from the Strong Heart Family Study. This study was aimed at identifying chromosomal (chr) loci affecting SNa in the same participants using a variance components decomposition‐based approach. Genome‐wide linkage analysis of SNa showed a strong signal on chr 2q for Dakota center data (LOD = 3.5) as well as for all centers combined (LOD = 2.9). We genotyped 88 SNPs in 2 candidate genes in the chr region of 2q: nephronophthisis1 ( NPHP1 ) and solute carrier family 9, subfamily 2, member 2 ( SLC9A2) . Measured genotype analysis of these SNPs showed significant association of SNa with SNP rs10496435 in NPHP1 and rs17775237 in SLC9A2 (p < 0.005). For both SNPs, the minor allele (A) was associated with lower SNa. Significant SNP by sex interaction effects on SNa were shown for both SNPs (p = 6 x 10 ‐3 ). When stratified by sex, men showed significant association with rs10496435 (p = 3 x 10 ‐4 ) whereas women showed with rs17775237 (p = 1 x10 ‐4 ). These results support the importance of the chr 2q region in the regulation of SNa and the evidence of SNP by sex interaction in the expression of genetic effects on SNa.