A study of candidate genotypes associated with dyspepsia in a U.S. community.
BACKGROUND
The role of genetic predisposition to the development of dyspepsia is unclear. Recently, a significant association was reported with CC genotype of GNbeta3.


OBJECTIVE
To explore the association of candidate genotypes altering adrenergic, serotonergic, CCKergic, and G protein functions, and dyspepsia in a sample from a U.S. community.


METHODS
Dyspeptics and healthy controls were identified among community respondents who had been randomly selected to complete validated questionnaires. Other diseases were excluded by face-to-face history and physical examination. Polymorphisms of candidate genes for alpha(2A), alpha(2C), 5-HT(1A), 5-HT(2A), 5-HT(2C), CCK-1 receptors and CCK promoter, GNbeta3 protein, and SERT-promoter (SERT-P) were studied. The association between polymorphisms and meal-related or meal-unrelated dyspepsia, high somatic symptom scores, and somatization were evaluated using Fisher's exact test.


RESULTS
DNA was available from 41 dyspeptics and 47 healthy controls from Olmsted County. Community dyspepsia unrelated to meals was associated with both homozygous GNbeta3 protein 825T and C alleles. There were no significant associations with meal-related dyspepsia. Using Rome II subgroups, the same genotype was associated with dysmotility-like and other dyspepsia. Higher somatization scores were not significantly associated with any of the candidate genes when considered as single factors.


CONCLUSIONS
Meal-unrelated dyspepsia in a U.S. community study is associated with the homozygous 825T or C alleles of GNbeta3 protein. Candidate genes controlling adrenergic, serotonergic, and CCKergic functions do not appear to be associated with dyspepsia.
Camilleri
Christopher E
CE
Gastroenterology Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Carlson
Paula J
PJ
Camilleri
Michael
M
Castillo
Emma J
EJ
Locke
G Richard
GR
Geno
Debra M
DM
Stephens
Debra A
DA
Zinsmeister
Alan R
AR
Urrutia
Raul
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC; D004415:Dyspepsia / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D019518:Postprandial Period; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D018925:Chemokines; D019742:Chemokines, CC; D044387:GTP-Binding Protein beta Subunits; D011518:Proto-Oncogene Proteins; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C414047:CCL28 protein, human; C493230:SLC6A4 protein, human; C067143:TAL1 protein, human