A genome-wide search for asthma susceptibility loci in ethnically diverse populations

Abstract

Asthma is an inflammatory airways disease associated with intermittent respiratory symptoms, bronchial hyper-responsiveness (BHR) and reversible airflow obstruction and is phenotypically heterogeneous. Patterns of clustering and segregation analyses in asthma families have suggested a genetic component to asthma. Previous studies reported linkage of BHR and atopy to chromosomes 5q (refs 7-9), 6p (refs 10-12), 11q (refs 13-15), 14q (ref. 16), and 12q (ref. 17) using candidate gene approaches. However, the relative roles of these genes in the pathogenesis of asthma or atopy are difficult to assess outside of the context of a genome-wide search. One genome-wide search in atopic sib pairs has been reported, however, only 12% of their subjects had asthma. We conducted a genome-wide search in 140 families with > or = 2 asthmatic sibs, from three racial groups and report evidence for linkage to six novel regions: 5p15 (P = 0.0008) and 17p11.1-q11.2 (P = 0.0015) in African Americans; 11p15 (P = 0.0089) and 19q13 (P = 0.0013) in Caucasians; 2q33 (P = 0.0005) and 21q21 (P = 0.0040) in Hispanics. Evidence for linkage was also detected in five regions previously reported to be linked to asthma-associated phenotypes: 5q23-31 (P = 0.0187), 6p21.3-23 (P = 0.0129), 12q14-24.2 (P = 0.0042), 13q21.3-qter (P = 0.0014), and 14q11.2-13 (P = 0.0062) in Caucasians and 12q14-24.2 (P = 0.0260) in Hispanics.

CD14 Promoter Polymorphisms in Atopic Families: Implications for Modulated Allergen-Specific Immunoglobulin E and G1 Responses

“…Baseline spirometry measures for forced expiratory volume at 1 s (FEV 1 ) were made according to the American Thoracic Society guidelines, followed by provocative methacholine challenges [18]. Bronchial hyperreactivity (BHR) was recorded if there was a decrease of 20% or more in FEV 1 after methacholine challenge (≤25 mg/ml maximum dosage).…”

“…Each subject was given a nurse-administered, standardized questionnaire, prepared according to the American Thoracic Society guidelines, regarding a history of asthma and other respiratory diseases as previously described [18]. Baseline spirometry measures for forced expiratory volume at 1 s (FEV 1 ) were made according to the American Thoracic Society guidelines, followed by provocative methacholine challenges [18].…”

“…Skin prick testing was done as previously described [18] using 14 standardized allergen extracts including ragweed, molds (3), trees (4), grasses (2), dust mites (2), and animal danders (2). A positive SPT result was recorded for a wheal area ≥9 mm 2 above the negative saline control.…”

A NOS1 Gene Polymorphism Associated with Asthma and Specific Immunoglobulin E Response to Mite Allergens in a Colombian Population

“…It is considered a multifactorial disorder involving complex interactions between genetic and environmental factors [4]. Several reasons make NOS1 an important candidate gene for asthma susceptibility, including its location on 12q14–24.2, a chromosomal region consistently reported to be linked to asthma and atopy in several studies [5,6,7,8] and the relationship of NO with asthma pathogenesis.…”

<i>Uteroglobin-Related Protein 1</i><i>(UGRP1)</i> Gene Polymorphisms and Atopic Asthma in the Indian Population

“…Various investigators have tried to reveal the genetic complexity of the disease via genome-wide linkage analysis and/or candidate gene approach. The chromosomal location 5q31 has been shown to harbor many promising candidate genes like IL4, IL5, IL13, or beta-2-adrenergic receptor gene (ADRB2) for asthma and other inflammatory diseases [4, 5]. …”