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Genetic variation in the beta‐2 adrenergic receptor (ADRB2) predicts functional gastrointestinal diagnoses and poorer health‐related quality of life
Author(s) -
Kushnir V. M.,
Cassell B.,
Gyawali C. P.,
Newberry R. D.,
Kibe P.,
Nix B. D.,
Sabzpoushan A.,
Kanuri N. D.,
Sayuk G. S.
Publication year - 2013
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12378
Subject(s) - medicine , quality of life (healthcare) , allele , gastroenterology , irritable bowel syndrome , medical diagnosis , pathology , genetics , gene , nursing , biology
Summary Background The beta‐2 adrenergic receptor ( ADRB 2) is an important target for epinephrine, a neurotransmitter in pain signalling. ADRB 2 haplotypes affect receptor expression and ligand response, and have been linked to painful non‐ GI disorders. Aims To assess whether ADRB 2 polymorphisms ( rs1042713 , rs1042714 ) are risk alleles for functional GI ( FGID ) and extraintestinal functional ( EIFD ) diagnoses, and whether ADRB 2 predicts GI symptoms and health‐related quality of life ( HRQOL ). Methods Of 398 subjects (49.6 ± 2.9 years, 68.0% female), 170 (42.5%) met Rome III criteria for ≥1 FGID [ IBS ( n = 139, 34.9%); functional dyspepsia ( FD , n = 136, 34.1%), functional chest pain ( FCP , n = 25, 6.2%)], while 228 were healthy controls. FGID subjects reported on bowel symptom severity and burden (10‐cm VAS ), frequency (days/last 2 weeks), EIFD , psychiatric diagnoses and HRQOL ( SF 36). Multivariable models determined the contribution of ADRB 2 polymorphisms to HRQOL , and mediational analyses assessed functional diagnoses as potential intermediates. Results rs1042714 minor G alleles were associated with FGID diagnoses ( OR 1.8; 95% CI 1.2–2.7; P = 0.009), particularly FD ( OR 2.1, 95% CI 1.3–3.3), with trends towards IBS ( P = 0.19) and FCP ( P = 0.06) diagnoses. Within IBS , G allele carriers had more severe bowel symptoms ( P = 0.025), and symptomatic days ( P = 0.009). G allele carriers had greater numbers of EIFD (1.0 ± 0.1 vs. 0.4 ± 0.07, P < 0.001) and poorer HRQOL . The effect of ADRB 2 on HRQOL was partially mediated by FGID , EIFD and psychiatric diagnoses. Conclusions ADRB 2 minor alleles at rs1042714 predict FGID and EIFD , and may influence bowel symptom severity and HRQOL . These findings provide indirect evidence of sympathetic nervous system role in FGID pathophysiology.