Two-dimensional, sex-specific autosomal linkage scan of the number of sodium pump sites.
OBJECTIVE
The sodium pump consists of the membrane-bound enzyme sodium/potassium-ATPase, which exchanges internal sodium ions for external potassium ions. Obesity, hypertension, and diabetes associate with the activity of the sodium pump, motivating gene discovery for sodium pump number.


METHODS
Variance components linkage analysis was applied to the number of red blood cell sodium pump sites measured by ouabain-binding assays on 1375 members of 46 Utah pedigrees. Both one-dimensional (1D) and two-dimensional (2D) autosome-wide linkage analyses of pump number were performed on the combined sample as well as separately on the male and female subsets.


RESULTS
Two significant 1D linkages were identified: on chromosome 1p13 in the combined sample [1D logarithm of odds (LOD) score = 3.76] and on chromosome 17p21 in the female subset (1D LOD score = 3.24). In addition, two significant 2D linkages were identified in the female subset: on chromosome 10q22 interacting with chromosome 18q11 (2D LOD score = 7.18) and on chromosome 13q21 interacting with chromosome 4q31 (2D LOD score = 6.05). Single-nucleotide polymorphism rs17376826 in neuropeptide Y receptor Y2, an obesity-associated gene and a candidate in the chromosome 4q31 linkage region, is associated with pump number (P = 0.046 in the combined sample and P = 0.042 in the female subset).


CONCLUSIONS
Pump number is influenced by multiple genes, possibly including neuropeptide Y receptor Y2.
Hasstedt
Sandra J
SJ
Department of Human Genetics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah 84112, USA. sandy@genetics.utah.edu
Xin
Yuanpei
Y
Hopkins
Paul N
PN
Hunt
Steven C
SC
D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002894:Chromosomes, Human, Pair 4; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D009765:Obesity / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012723:Sex; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
D000254:Sodium-Potassium-Exchanging ATPase