Regional association-based fine-mapping for sodium-lithium countertransport on chromosome 10.
BACKGROUND
Increased erythrocyte sodium-lithium countertransport (SLC) has been observed in patients with essential hypertension. Consistent evidence of genetic linkage was shown for SLC on chromosome 10, and a region of interest was localized between 26 and 56 Mb.


METHODS
This study surveyed single nucleotide polymorphisms (SNPs) in 54 genes that reside in the region of interest, and investigated their association with SLC and blood pressure. These SNPs were genotyped in 1,133 non-Hispanic white individuals from 255 pedigrees comprising the second phase of the Rochester Family Heart Study. The variance-components-based genetics software package SOLAR was used for evaluating whether an SNP contributed to a significant fraction of the trait heritability.


RESULTS
Of the 77 SNPs surveyed in this study across the region of interest, four SNPs were associated with SLC (P < 0.04), five SNPs were associated with blood pressure (P < 0.04), and two SNPs in mannose-binding lectin 2 (MBL2) were associated with both phenotypes. In general, the pairwise linkage disequilibrium among the genotyped SNPs was low.


CONCLUSIONS
This fine-mapping survey of genetic variation in a linkage region of interest provides overall support for association-mapping for SLC on chromosome 10. Genes significantly associated with systolic blood pressure and/or SLC in these families will be prioritized for future studies.
Morrison
Alanna C
AC
Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA. Alanna.C.Morrison@uth.tmc.edu
Boerwinkle
Eric
E
Turner
Stephen T
ST
Ferrell
Robert E
RE
D000293:Adolescent; D000328:Adult; D000368:Aged; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015810:Linkage Disequilibrium; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D008910:Minnesota; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D017920:Antiporters; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C045885:sodium-lithium countertransporter