Contributing role of metabolic genes <i>APOE, FTO</i>, and <i>LPL</i> in the development of atrial fibrillation: insights from a case-control study

Rafaqat, Saira; Sharif, Saima; Naz, Shagufta; Patoulias, Dimitrios; Klisic, Aleksandra

doi:10.1590/1806-9282.20240263

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Revista da Associação Médica Brasileira

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Original Article • Rev. Assoc. Med. Bras. 70 (8) • 2024 • https://doi.org/10.1590/1806-9282.20240263 copy

Contributing role of metabolic genes APOE, FTO, and LPL in the development of atrial fibrillation: insights from a case-control study

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF).

METHODS:

A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS.

RESULTS:

The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS.

CONCLUSION:

The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.

KEYWORDS:
Gene expression profile; Atrial fibrillation; Metabolic syndrome

Clinical parameters		Control group (n=230)	AF without the MetS group (n=230)	AF with the MetS group (n=230)
Age (years)		57.86±11.32	58.40±11.23	58.40±11.23
Gender, n (%)
	Male	108 (47)	120 (52)	106 (70)
	Female	122 (53)	110 (48)	124 (54)
SBP (mmHg)		112.43±8.10	126.45±21.42	134.30±36.52**
DBP (mmHg)		85.34±5.80	83.22±13.48	93.04±18.07**
Heart rate (bpm)		68.08±6.79	121.45±30.60	116.80±30.83**
BMI (kg/m²2 Rafaqat S, Sharif S, Majeed M, Naz S, Saqib M, Manzoor F. Association of adiponectin gene expression with atrial fibrillation in a Pakistani populace. Sci Rep. 2023;13(1):22589. https://doi.org/10.1038/s41598-023-46388-2 https://doi.org/10.1038/s41598-023-46388... )		23.37±2.12	29.29±5.55	28.22±10.33**
FBG (mg/dL)		89.60±8.77	122.39±38.56	140.77±50.15**
WHR		0.81±0.05	0.80±0.05	0.93±0.06**
TC (mg/dL)		179.34±18.57	189.29±166.35	187.73±58.73
HDL-C (mg/dL)		56.66±12.53	39.84±23.29	10.68±1.72**
TG (mg/dL)		84.14±66.169	135.01±68.13	156.94±55.99**
LDL-C (mg/dL)		167.88±43.18	185.82±167.82	189.43±74.17
cTnI (ng/mL)		6.40±3.45	0.93±2.19	1.08±3.03**
CK-MB (U/L)		19.49±2.41	55.60±78.81	79.11±84.02**
CPK (U/L)		118.68±28.64	1136.52±4325.53	675.18±3096.93**
Expression of APOE gene (arbitrary units)		3.41 fold	0.66 fold	1.59 fold**
Expression of FTO gene (arbitrary units)		3.84 fold	1.37 fold	1.14 fold**
Expression of LPL gene (arbitrary units)		2.41 fold	0.01 fold	0.24 fold**

Clinical parameters	r-value of Exp APOE gene			r-value of Exp FTO gene			r-value of Exp LPL gene
Clinical parameters	Control group	AF without MetS group	AF with MetS group	Control group	AF without MetS group	AF with MetS group	Control group	AF without MetS group	AF with MetS group
Age (years)	-0.004	0.020	0.071	0.072	0.089	-0.015	0.025	0.042	-0.041
SBP (mmHg)	-0.109	-0.073	-0.013	0.043	-0.013	-0.021	-0.092	0.024	0.136^* * Correlation is significant at 0.05 level (two-tailed).
DBP (mmHg)	-0.029	0.026	-0.022	-0.067	0.033	0.044	-0.029	0.048	-0.038
Heart rate (bpm)	0.092	0.119	0.028	-0.007	-0.025	0.097	-0.125	0.086	-0.307^ Correlation is significant at 0.01 level (two-tailed).
BMI (kg/m²2 Rafaqat S, Sharif S, Majeed M, Naz S, Saqib M, Manzoor F. Association of adiponectin gene expression with atrial fibrillation in a Pakistani populace. Sci Rep. 2023;13(1):22589. https://doi.org/10.1038/s41598-023-46388-2 https://doi.org/10.1038/s41598-023-46388... )	-0.075	-0.005	-0.046	-0.047	0.044	0.015	0.002	-0.180^ Correlation is significant at 0.01 level (two-tailed).	0.014
FBG (mg/dL)	0.014	-0.010	-0.056	-0.017	0.007	-0.168^* * Correlation is significant at 0.05 level (two-tailed).	-0.044	-0.024	0.041
HDL-C (mg/dL)	-0.035	0.033	0.110	0.089	-0.065	0.009	-0.158^* * Correlation is significant at 0.05 level (two-tailed).	0.047	0.137^* * Correlation is significant at 0.05 level (two-tailed).
TG (mg/dL)	0.013	0.058	-0.034	0.032	-0.045	0.070	-0.014	0.051	-0.046
cTnI (ng/mL)	-0.252^ Correlation is significant at 0.01 level (two-tailed).	0.039	0.106	-0.041	-0.001	0.139^* * Correlation is significant at 0.05 level (two-tailed).	-0.347^ Correlation is significant at 0.01 level (two-tailed).	-0.015	-0.001
CK-MB (U/L)	-0.099	0.028	-0.118	-0.114	-0.089	-0.029	-0.036	0.137^* * Correlation is significant at 0.05 level (two-tailed).	0.015
CPK (U/L)	-0.102	-0.023	0.001	-0.092	-0.050	-0.039	-0.062	0.118	-0.015
Expression of APOE gene	-	-	-	0.015	0.043	0.004	0.381^* * Correlation is significant at 0.05 level (two-tailed).	-0.037	-0.108
Expression of FTO gene	0.015	0.043	0.004	-	-	-	-0.020	-0.102	-0.163^* * Correlation is significant at 0.05 level (two-tailed).
Expression of LPL gene	0.381^ Correlation is significant at 0.01 level (two-tailed).	-0.037	-0.108	0.020	-0.102	-0.163^* * Correlation is significant at 0.05 level (two-tailed).	-	-	-

Variable		B	95% CI		SE B	β	p-value	R²2 Rafaqat S, Sharif S, Majeed M, Naz S, Saqib M, Manzoor F. Association of adiponectin gene expression with atrial fibrillation in a Pakistani populace. Sci Rep. 2023;13(1):22589. https://doi.org/10.1038/s41598-023-46388-2 https://doi.org/10.1038/s41598-023-46388...	ΔR²2 Rafaqat S, Sharif S, Majeed M, Naz S, Saqib M, Manzoor F. Association of adiponectin gene expression with atrial fibrillation in a Pakistani populace. Sci Rep. 2023;13(1):22589. https://doi.org/10.1038/s41598-023-46388-2 https://doi.org/10.1038/s41598-023-46388...	Sig. F change
Variable		B	LL	UL	SE B	β	p-value			Sig. F change
AF without MetS group (Expression of LPL gene)
Model 1								0.033	0.033	0.006
Constant		0.057	0.030	0.083	0.013		0.000
BMI		-0.001	-0.002	0.000	0.000	-0.180	0.006
AF with MetS group (Expression of FTO gene)
Model 1								0.028	0.028	0.011
	Constant	1.941	1.301	2.582	0.325		0.000
	FBG	-0.006	-0.010	-0.001	0.002	-0.168	0.011
Model 2								0.053	0.025	0.016
	Constant	2.121	1.470	2.771	0.330		0.000
	FBG	-0.005	-0.010	-0.001	0.002	-0.162	0.013
	Exp of LPL gene	0.869	-1.576	-0.163	0.359	-0.157	0.016
Model 3								0.076	0.023	0.018
	Constant	2.086	1.442	2.731	0.327		0.000
	FBG	-0.006	-0.010	-0.002	0.002	-0.174	0.007
	Exp of LPL gene	-0.866	-1.565	-0.166	0.355	-0.158	0.016
	cTnI	0.084	0.015	0.154	0.035	0.153	0.018
(Expression of LPL gene)
Model 1								0.094	0.094	0.001
	Constant	0.592	0.446	0.739	0.074		0.000
	Heart rate	-0.003	-0.004	-0.002	0.001	-0.307	0.000
Model 2								0.112	0.018	0.033
	Constant	0.605	0.459	0.751	0.074		0.000
	Heart rate	-0.003	-0.004	-0.002	0.001	-0.294	0.000
	Exp of FTO gene	-0.024	-0.047	-0.002	0.011	-0.135	0.033
Model 3								0.129	0.017	0.035
	Constant	0.458	0.259	0.658	0.101		0.000
	Heart rate	-0.003	-0.004	-0.002	0.001	-0.293	0.000
	Exp of FTO gene	-0.024	-0.046	-0.002	0.011	-0.132	0.035
	SBP	0.001	0.000	0.002	0.001	0.132	0.035

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[1] *Corresponding author: aleksandranklisic@gmail.com