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Aging and disease    2017, Vol. 8 Issue (4) : 434-441     DOI: 10.14336/AD.2016.1202
Original Article |
P2X7 Receptor and APOE Polymorphisms and Survival from Heart Failure: A Prospective Study in Frail Patients in a Geriatric Unit
Pasqualetti Giuseppe, Seghieri Marta, Santini Eleonora, Rossi Chiara, Vitolo Edoardo, Giannini Livia, Malatesta Maria Giovanna, Calsolaro Valeria, Monzani Fabio*, Solini Anna*
Department of Clinical and Experimental Medicine University of Pisa, Pisa, Italy
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Abstract  

Heart failure (HF) is one of the most frequent cause of hospitalization in elderly and often coexists with concurrent geriatric syndromes, like cognitive disturbances; various pathophysiological mechanisms are shared by HF and cognitive decline, notably a substrate of low-grade inflammation. We investigated whether SNPs in the purinergic receptor (P2X7R) and apolipoprotein (APO) E genes, both involved in a series of inflammatory responses, are associated to HF or cognitive impairment and are able to predict post-discharge mortality in the elderly. We prospectively analyzed 198 patients (age 85 ± 8 years, predominantly females) admitted to a Geriatric unit for acute HF, whose diagnosis was based on clinical signs, brain natriuretic peptide (BNP) values and ecocardiography in uncertain diagnosis (BNP values between 100 and 400 pg/mL); cognitive performance was assesed by Short Portable Mental Status Questionnaire (SPMSQ). In all the participants, SNPs rs208294 and rs3751143 for P2X7R gene and rs429558 and rs7412 for APOE gene were assessed. Information on all-cause mortality was adjudicated by medical records review 36 months after discharge. We found no relationship between P2X7R and APOE polymorphisms and 36-month post-discharge mortality; a better outcome for overall survival was observed in patients with BNP values below the median (281 pg/mL) (p=0.002) persisting after adjustment for renal function and age, and in those with cognitive impairment (p<0.001). Patients harboring APOE-ε4 genotype showed higher BNP concentrations than noncarriers (1289.9 ± 226.9 vs 580.5 ± 90.2 pg/mL respectively,p=0.004), whereas none of the studied SNPs were associated to impairment in cognitive performance. In conclusion, neither P2X7R or APOE genotype seem to predict long-term mortality in elderly patients. Interestingly, APOE-ε4 genotype was associated to higher BNP values, suggesting a putative interaction between genetic and biochemical markers in identifying people at risk for HF.

Keywords heart failure      brain natriuretic peptide      P2X7 receptor      apolipoprotein E      polymorphisms      long-term mortality     
Corresponding Authors: Monzani Fabio,Solini Anna   
About author:

these authors equally contributed to this work

Issue Date: 01 August 2017
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Pasqualetti Giuseppe
Seghieri Marta
Santini Eleonora
Rossi Chiara
Vitolo Edoardo
Giannini Livia
Malatesta Maria Giovanna
Calsolaro Valeria
Monzani Fabio
Solini Anna
Cite this article:   
Pasqualetti Giuseppe,Seghieri Marta,Santini Eleonora, et al. P2X7 Receptor and APOE Polymorphisms and Survival from Heart Failure: A Prospective Study in Frail Patients in a Geriatric Unit[J]. Aging and disease, 2017, 8(4): 434-441.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2016.1202     OR     http://www.aginganddisease.org/EN/Y2017/V8/I4/434
Age (years)85 ± 8
Sex (M/F)61/137
BMI (kg/m2)24.7 ± 4.5
SBP (mmHg)136.7 ± 21.7
DBP (mmHg)74.8 ± 12.4
Comorbidity (Charlson Index)7.8 ± 2.0
Severe dependence (ADL)121 (61.2)
Cognitive impairment (SPMSQ)100 (50.6)
NYHA functional class
I53 (27)
II89 (45)
III54 (27)
IV2 (1)
Medications, n (%)
RAAS inhibitors109 (55)
Beta blockers75 (38)
Diuretics48 (24)
Anti-platelets46 (23)
Table 1A  Baseline characteristics of the study group (n=198).
Red blood cell count (x106/mmc)3.93 ± 0.92
Hemoglobin (g/dL)11.1 ± 3.0
White blood cell count (x103/mmc)7.8 ± 1.6
Platelets (x103/mmc)232 (130)
Fasting plasma glucose (mg/dL)115.7 ± 23.6
Total cholesterol (mg/dL)163.7 ± 13.7
Triglycerides (mg/dL)124.7 ± 33.5
Fibrinogen (mg/dL)319 (178)
Creatinine (mg/dL)1.15 ± 0.63
Estimated glomerular filtration rate (by MDRD, mL/min/1.73m2)58 ± 37
Hs-PCR (mg/dL)4.66 (8.63)
BNP (pg/mL)281 (689)
Table 1B  Biochemical variables of the study group (n=198).
A
SNPsBNP (pg/mL)p
P2X7R rs3751143A carriers C carriers702.0 ± 115.0 674.3 ± 167.00.892
P2X7R
rs208294
C carriers
T carriers
626.2 ± 162.6
721.6 ± 103.4
0.621
APOE rs429358 rs7412ε4 carriers ε4 noncarriers1289.9 ± 226.9 580.5 ± 90.20.004
B
SNPsCognitive impairment (% of patients)p
P2X7R rs3751143A carriers C carriers49 490.892
P2X7R
rs208294
C carriers
T carriers
46
50
0.621
APOE
rs429358 rs7412
ε4 carriers ε4 noncarriers63 370.07
Table 2  Association between genotypes and BNP value (A) or percentage of cognitive impairment (B) in the study population.
Figure 1.  Overall survival curves of all the patients according to genetic profiles of the studied polymorphisms

Survival curves were calculated with the Kaplan Meier method.

SNPGenotypeNAlleleN%HWE (p)
P2X7R
rs208294
T-T
C-T C-C
38
100 52
C
T
152
138
0.90
0.10
0.42
P2X7R
rs3751143
A-A
C-A C-C
111
55 8
A
C
166
63
0.72
0.28
0.72
APOE
rs7412
C-C
C-T
181
17
C
T
198
17
0.92
0.08
0.53
APOE
rs429358
T-T
C-T
157
32
C
T
32
189
0.14
0.86
0.20
Suppl Table A  Genotypes, allele frequencies and Hardy-Weinberg Equilibrium (HWE) of the studied polymorphisms
Β coefficientp
BNP0.00030.032
Age0.0460.084
Sex (f)-0.1620.340
Charlson comorbidity index0.0790.257
Suppl Table B  Proportional hazards regression analysis showing BNP impact on reduced overall survival
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