Association of Met439Thr substitution in heat shock protein 70 gene with postoperative atrial fibrillation and serum HSP70 protein levels.
BACKGROUND
Atrial fibrillation (AF) is a common arrhythmia encountered following cardiac surgery. Previously, we have shown that higher expression of heat shock protein (HSP) 70 was associated with decreased incidence of postoperative AF (PoAF), suggestive of an antiarrhythmic role.


OBJECTIVE
We have hypothesised that Met493Thr substitution of one of the important hsp70 genes may cause loss of these protective antiarrhythmic effects. We therefore set out to examine the influence of hsp70 genotype on the incidence of PoAF.


RESULTS
We prospectively recruited 244 Caucasian patients undergoing elective coronary artery bypass surgery. The median age was 65 years (40-80 years). PoAF was defined as the characteristic arrhythmia lasting for at least 15 min, occurring within first week following surgery and requiring treatment. This occurred in 48 patients (19.7%). Validated Met493Thr substitution in hsp70-Hom was determined using established techniques. Of 244 patients, genotype was determined for 242 cases. The three genotypes (MM, MT, and TT) were present at frequencies of 0.66, 0.31, and 0.03, respectively, and were in Hardy-Weinberg equilibrium. In unifactorial analysis patients carrier or homozygous for 493Thr mutation had significantly higher incidence of PoAF (Pearson chi(2) = 4.3, p = 0.037). Multivariate analysis confirmed the positive association of hsp70-Hom with PoAF (OR, 2.43; p = 0.016) independent of age, sex, previous myocardial infarction, number of distal anastomoses, and duration of ventilation, respectively. Serum HSP70 was ranging from 0.74 to 31.91 ng/ml (median, 2.89) and was not correlated with PoAF. Presence of 493Thr mutation was also significantly correlated with higher levels of serum HSP70 (p = 0.009).


CONCLUSIONS
Our data show that a mutation in hsp70-Hom gene is associated with higher incidence of PoAF. These findings are consistent with our previous results and may suggest that patients harbouring this substitution will have less endogenous myocardial protection against AF in stressful situations.
Afzal
Ali R
AR
Department of Clinical Developmental Sciences, St George's University of London, London, UK. a_r_afzal@yahoo.co.uk
Mandal
Kaushik
K
Nyamweya
Samuel
S
Foteinos
Georgios
G
Poloniecki
Jan
J
Camm
A John
AJ
Jahangiri
Marjan
M
Xu
Qingbo
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000379:methods; D003327:Coronary Disease / Q000175:diagnosis / Q000601:surgery; D017558:Elective Surgical Procedures; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000175:diagnosis; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D005819:Genetic Markers; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C121993:HSPA4 protein, human