Gene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican-Americans.

TitleGene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican-Americans.
Publication TypeJournal Article
Year of Publication2009
AuthorsMontasser, ME, Shimmin, LC, Hanis, CL, Boerwinkle, E, Hixson, JE
JournalJ Hypertens
Volume27
Issue3
Pagination491-501
Date Published2009 Mar
ISSN1473-5598
KeywordsAged, Blood Pressure, Chromosomes, Human, Pair 15, Female, Genetic Linkage, Humans, Hypertension, Lod Score, Male, Mexican Americans, Microsatellite Repeats, Middle Aged, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Smoking, Statistics, Nonparametric, Texas
Abstract

OBJECTIVE: Our objective was to investigate the influence of gene by smoking (GxS) interaction on hypertension and blood pressure (BP) using genome-wide linkage analysis in Mexican-Americans, followed by single nucleotide polymorphism (SNP) fine mapping of candidate genes in the linked chromosomal region.METHODS: We used nonparametric methods to test for linkage of microsatellites with hypertension and BP measures in smokers, nonsmokers, and the combined group. To begin fine mapping of a major quantitative trait locus (QTL) for systolic blood pressure (SBP) on chromosome 15q that showed strong evidence for GxS interaction, we genotyped 55 SNPs in nine candidate genes for association studies using two population-based statistical methods.RESULTS: The strongest evidence for GxS interaction (P = 0.0004) was found for SBP on chromosome 15q, where a major QTL (LOD = 3.36) was identified only in nonsmokers. Follow-up studies identified three SNPs in three genes (ANPEP, IGF1R, and SLCO3A1) that showed associations with SBP only in nonsmokers, cumulatively accounting for a 7 mmHg increase in SBP. However, conditional linkage analyses that accounted for phenotypic effects of these SNPs only slightly reduced the original LOD score.CONCLUSION: The detection of a major QTL on chromosome 15q for SBP in nonsmokers indicates the presence of loci that influence BP via GxS interactions. However, identification of the genes that underlie such QTL effects remains a challenge. Although we found three candidate genes that showed significant associations with SBP in nonsmokers, further studies are required to identify the gene(s) that underlie the chromosome 15q QTL that influences SBP via GxS interactions.

Alternate JournalJ. Hypertens.
PubMed ID19330903
PubMed Central IDPMC2664514
Grant ListR01 HL039107 / HL / NHLBI NIH HHS / United States
U01 HL054481-13 / HL / NHLBI NIH HHS / United States
HL-051021 / HL / NHLBI NIH HHS / United States
U01 HL054504 / HL / NHLBI NIH HHS / United States
U10 HL054504 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
HL-039107 / HL / NHLBI NIH HHS / United States
U01 HL054504-10 / HL / NHLBI NIH HHS / United States
HL-54504 / HL / NHLBI NIH HHS / United States
HL-54457 / HL / NHLBI NIH HHS / United States
U01 HL054481 / HL / NHLBI NIH HHS / United States
R37 HL051021-15 / HL / NHLBI NIH HHS / United States
R37 HL051021 / HL / NHLBI NIH HHS / United States