Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy

doi:10.4240/wjgs.v15.i10.2154

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World Journal of Gastrointestinal Surgery

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1948-9366

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Gastrointest Surg. Oct 27, 2023; 15(10): 2154-2170
Published online Oct 27, 2023. doi: 10.4240/wjgs.v15.i10.2154

Table 1 Baseline and clinical parameters of patients with ≥ 30% vs < 30% heart rate variability, n (%)

Variable	HRV ≥ 30%	HRV < 30%	χ²	P value
Sex			1.828	0.18
Female	9 (16.36)	46 (83.64)
Male	13 (9.49)	124 (90.51)
Age (yr)			0.098	0.75
< 60	5 (14.29)	30 (85.71)
≥ 60	17 (10.83)	140 (89.17)
Smoking status			0.592	0.44
No	20 (12.58)	139 (87.42)
Yes	2 (6.06)	31 (93.94)
Hypertension			0.213	0.64
No	13 (10.66)	109 (89.34)
Yes	9 (12.86)	61 (87.14)
Diabetes			0.299	0.58
No	19 (10.80)	157 (89.20)
Yes	3 (18.75)	13 (81.25)
Blood type			0.964	0.81
A	9 (12.33)	64 (87.67)
AB	1 (5.00)	19 (95.00)
B	5 (11.36)	39 (88.64)
O	7 (12.73)	49 (87.27)
Thyroid function			0.005	0.95
Normal	20 (11.70)	151 (88.30)
Abnormal	2 (9.52)	19 (90.48)

All P values are more than 0.05. HRV: Heart rate variability.

Table 2 Baseline and clinical parameters of patients with ≥ 15% vs < 15% heart rate variability, n (%)

Variable	HRV ≥ 15%	HRV < 15%	χ²	P value
Sex			0.015	0.90
Female	21 (38.18)	34 (61.82)
Male	51 (37.23)	86 (62.77)
Age (yr)			1.232	0.27
< 60	16 (45.71)	19 (54.29)
≥ 60	56 (35.67)	101 (64.33)
Smoking status			0.412	0.52
No	58 (36.48)	101 (63.52)
Yes	14 (42.42)	19 (57.58)
Hypertension			0.006	0.94
No	46 (37.70)	76 (62.30)
Yes	26 (37.14)	44 (62.86)
Diabetes			2.618	0.11
No	63 (35.80)	113 (64.20)
Yes	9 (56.25)	7 (43.75)
Blood type			1.803	0.61
A	27 (36.99)	46 (63.01)
AB	5 (25.00)	15 (75.00)
B	17 (38.64)	27 (61.36)
O	23 (41.82)	32 (58.18)
Thyroid function			0.289	0.59
Normal	63 (36.84)	108 (63.16)
Abnormal	9 (42.86)	12 (57.14)

All P values are more than 0.05. HRV: Heart rate variability.

Table 3 Comparison of genotype and allele dissemination of single nucleotide polymorphisms in patients with ≥ 30% vs < 30% heart rate variability, n (%)

SNP	HRV ≥ 30%	HRV < 30%	χ²	P value	OR (95%CI)
TEP1 (rs938886)			1.30	0.52
GG	9 (10.00)	81 (90.00)			1.00 (Reference)
GC	12 (14.12)	73 (85.88)			1.63 (0.63, 4.20)
CC	1 (5.88)	16 (94.12)			0.72 (0.081, 6.39)
			0.016	0.90
G	30 (11.32)	235 (88.68)			1.00 (Reference)
C	14 (11.76)	105 (88.24)			1.16 (0.58, 2.31)
TEP1 (rs1713449)			1.54	0.46
CC	9 (10.11)	80 (89.89)			1.00 (Reference)
CT	12 (14.29)	72 (85.71)			1.63 (0.63, 4.21)
TT	1 (5.26)	18 (94.74)			0.62 (0.071, 5.43)
			0.0001	0.99
C	30 (11.45)	232 (88.55)			1.00 (Reference)
T	14 (11.48)	108 (88.52)			1.11 (0.56, 2.22)
RECQL5 (rs820196)			3.93	0.14
TT	7 (8.05)	80 (91.95)			1.00 (Reference)
TC	14 (16.47)	71 (83.53)			2.39 (0.90, 6.33)
CC	1 (5.00)	19 (95.00)			0.65 (0.073, 5.72)
			0.33	0.57
T	28 (10.81)	231 (89.19)			1.00 (Reference)
C	16 (12.80)	109 (87.20)			1.27 (0.66, 2.47)

All P values are more than 0.05. Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. Two covariates with missing values were dropped. SNP: Single nucleotide polymorphisms; TEP1: Telomerase-associated protein 1; HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval; RECQL5: RecQ like helicase 5.

Table 4 Comparison of genotype and allele frequencies of single nucleotide polymorphisms in patients with ≥ 15% vs < 15% heart rate variability, n (%)

SNP	HRV ≥ 15%	HRV < 15%	χ²	P value	OR (95%CI)
TEP1 (rs938886)			1.56	0.46
GG	30 (33.33)	60 (66.67)			1.00 (Reference)
GC	34 (40.00)	51 (60.00)			1.34 (0.72, 2.52)
CC	8 (47.06)	9 (52.94)			1.74 (0.59, 5.15)
			1.50	0.22
G	94 (35.47)	171 (64.53)			1.00 (Reference)
C	50 (42.02)	69 (57.98)			1.30 (0.83, 2.04)
TEP1 (rs1713449)			2.02	0.36
CC	29 (32.58)	60 (67.42)			1.00 (Reference)
CT	34 (40.48)	50 (59.52)			1.42 (0.75, 2.67)
TT	9 (47.37)	10 (52.63)			1.85 (0.66, 5.21)
			2.00	0.16
C	92 (35.11)	170 (64.89)			1.00 (Reference)
T	52 (42.62)	70 (57.38)			1.36 (0.87, 2.13)
RECQL5 (rs820196)			6.20	0.045
TT	27 (31.03)	60 (68.97)			1.00 (Reference)
TC	40 (47.06)	45 (52.94)			1.97 (1.05, 3.70)^a
CC	5 (25.00)	15 (75.00)			0.69 (0.22, 2.13)
			0.49	0.48
T	94 (36.29)	165 (63.71)			1.00 (Reference)
C	50 (40.00)	75 (60.00)			1.15 (0.74, 1.78)

^aP < 0.05 vs TT.

Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. Two covariates with missing values were dropped. SNP: Single nucleotide polymorphism; TEP1: Telomerase-associated protein 1; HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval; RECQL5: RecQ like helicase 5.

Table 5 Association of telomerase-associated protein 1 and RecQ like helicase 5 polymorphisms with heart rate variability ≥ 30% under different inheritance models

Inheritance model	TEP1 (rs938886)		TEP1 (rs1713449)		RECQL5 (rs820196)
Inheritance model	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Codominant
Aa vs AA	1.67 (0.64, 4.31)	0.293	1.67 (0.65, 4.34)	0.289	2.35 (0.88, 6.24)	0.087
aa vs AA	0.62 (0.068, 5.70)	0.675	0.54 (0.060, 4.84)	0.582	0.58 (0.065, 5.21)	0.628
Dominant (Aa + aa vs AA)	1.49 (0.59, 3.76)	0.403	1.46 (0.58, 3.68)	0.429	2.02 (0.78, 5.25)	0.151
Overdominant (Aa vs AA + aa)	1.69 (0.68, 4.24)	0.261	1.74 (0.69, 4.35)	0.238	2.54 (0.99, 6.49)	0.051
Recessive (aa vs Aa + AA)	0.56 (0.067, 4.64)	0.590	0.48 (0.059, 3.92)	0.494	0.41 (0.050, 3.27)	0.396
Additive (AA vs Aa vs aa)	1.18 (0.57, 2.42)	0.657	1.12 (0.55, 2.27)	0.752	1.28 (0.65, 2.51)	0.472

All P values are more than 0.05. Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. A: Major allele; a: Minor allele; TEP1: Telomerase-associated protein 1; OR: Odds ratio; CI: Confidence interval; RECQL5: RecQ like helicase 5.

Table 6 Association of telomerase-associated protein 1 and RecQ like helicase 5 polymorphisms with heart rate variability ≥ 15% under different inheritance models

Inheritance model	TEP1 (rs938886)		TEP1 (rs1713449)		RECQL5 (rs820196)
Inheritance model	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Codominant
Aa vs AA	1.36 (0.72, 2.55)	0.341	1.43 (0.76, 2.69)	0.271	2.00 (1.06, 3.76)	0.031^a
aa vs AA	1.31 (0.75, 2.29)	0.345	1.34 (0.79, 2.28)	0.279	0.82 (0.46, 1.45)	0.492
Dominant (Aa + aa vs AA)	1.40 (0.77, 2.56)	0.273	1.49 (0.81, 2.72)	0.196	1.64 (0.90, 2.98)	0.109
Overdominant (Aa vs AA + aa)	1.23 (0.67, 2.23)	0.506	1.27 (0.70, 2.31)	0.441	2.10 (1.15, 3.84)	0.016^b
Recessive (aa vs Aa + AA)	1.50 (0.53, 4.25)	0.442	1.56 (0.58, 4.16)	0.378	0.50 (0.17, 1.46)	0.202
Additive (AA vs Aa vs aa)	1.33 (0.83, 2.12)	0.233	1.38 (0.88, 2.18)	0.166	1.15 (0.74, 1.80)	0.537

^aP < 0.05 vs TT.

^bP < 0.05 vs TT + CC.

Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. A: Major allele; a: Minor allele; TEP1: Telomerase-associated protein 1; OR: Odds ratio; CI: Confidence interval; RECQL5: RecQ like helicase 5.

Table 7 Association of telomerase-associated protein 1 haplotypes with heart rate variability risk using a 30% heart rate variability cutoff

TEP1 (rs938886)	TEP1 (rs1713449)	Frequency	HRV ≥ 30% (n = 22)	HRV < 30% (n = 170)	OR (95%CI)	P value
G	C	0.682	30 (11.45)	232 (88.55)	1.00 (Reference)	-
C	T	0.310	14 (11.76)	105 (88.24)	1.15 (0.58, 2.28)	0.70
G	T	0.008	0 (00.00)	3 (100.00)	-	-

All P values are more than 0.05. Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. TEP1: Telomerase-associated protein 1; HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval.

Table 8 Association of telomerase-associated protein 1 haplotypes with heart rate variability risk using a 15% heart rate variability cutoff

TEP1 (rs938886)	TEP1 (rs1713449)	Frequency	HRV ≥ 15% (n = 72)	HRV < 15% (n = 120)	OR (95%CI)	P value
G	C	0.682	92 (35.11)	170 (64.89)	1.00 (Reference)	-
C	T	0.310	50 (42.02)	69 (57.98)	1.33 (0.85-2.08)	0.22
G	T	0.008	2 (66.67)	1 (33.33)	4.13 (0.37, 46.59)	0.25

Table 9 Best single nucleotide polymorphism-single nucleotide polymorphism interaction models identified by generalized multifactor dimensionality reduction with covariable adjustment (heart rate variability cutoff value = 30%)

Best model	Training balanced accuracy	Testing balanced accuracy	Cross-validation consistency	P value
rs820196	0.6116	0.6127	10/10	0.032^a
rs938886, rs820196	0.6495	0.5782	10/10	0.151
rs938886, rs820196, rs1713449	0.6495	0.5753	10/10	0.168

^aP < 0.05 means the one-locus model of RecQ like helicase 5 rs820196 is the best model for predicting heart rate variability risk.

Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function.

Table 10 Association analysis of the interaction between different genotypes of single nucleotide polymorphism loci and a risk of heart rate variability cutoff value ≥ 30%

SNP genotypes			HRV ≥ 30% (n = 22)	HRV < 30% (n = 170)	OR (95%CI)	P value
rs938886 rs820196
GG	TT		3 (6.67)	42 (93.33)	1.00 (Reference)	-
GG	TC		5 (14.29)	30 (85.71)	2.91 (0.63, 13.55)	0.17
GG	CC		1 (10.00)	9 (90.00)	2.19 (0.19, 25.37)	0.53
GC	TT		3 (8.11)	34 (91.89)	1.65 (0.31, 8.74)	0.56
GC	TC		9 (22.50)	31 (77.50)	6.16 (1.53, 24.83)	0.01^a
CC	TT		1 (20.00)	4 (80.00)	5.84 (0.46, 74.57)	0.17
Others			0 (0.00)	20 (100.00)	-	-
rs938886 rs820196 rs1713449
GG	TT	CC	3 (6.82)	41 (93.18)	1.00 (Reference)	-
GG	TC	CC	5 (14.29)	30 (85.71)	2.97 (0.64, 13.79)	0.17
GG	CC	CC	1 (10.00)	9 (90.00)	2.23 (0.19, 25.87)	0.52
GC	TT	CT	3 (8.33)	33 (91.67)	1.73 (0.33, 9.18)	0.52
GC	TC	CT	9 (22.50)	31 (77.50)	6.27 (1.56, 25.28)	0.01^b
CC	TT	TT	1 (20.00)	4 (80.00)	5.94 (0.47, 75.98)	0.17
Others			0 (0.00)	22 (100.00)	-	-

^aP < 0.05 vs GG-TT.

^bP < 0.05 vs GG-TT-CC.

Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function. SNP: Single nucleotide polymorphism; HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval.

Table 11 Single nucleotide polymorphism-smoking, single nucleotide polymorphism -hypertension, and single nucleotide polymorphism-thyroid function interaction models in patients with heart rate variability ≥ 30% evaluated with the generalized multifactor dimensionality reduction approach

Best model	Training balanced accuracy	Testing balanced accuracy	CVC	P value
SNP-smoking interaction¹
Smoking	0.5265	0.5135	10/10	0.263
rs820196-smoking	0.6281	0.6021	10/10	0.045^a
rs938886-rs820196-smoking	0.6703	0.5947	8/10	0.099
SNP-hypertension interaction²
Hypertension	0.5292	0.3308	10/10	0.800
rs820196-hypertension	0.6117	0.5648	10/10	0.190
rs820196-rs1713449-hypertension	0.6996	0.5063	8/10	0.426
SNP-thyroid function interaction³
Thyroid function	0.5123	0.4980	10/10	0.194
rs820196-thyroid function	0.6263	0.5895	10/10	0.104
rs938886-rs820196-thyroid function	0.6665	0.5727	8/10	0.153

^aP < 0.05 means rs820196-smoking two-factor model associated with HRV ≥ 30%.

¹Adjusted for age, gender, hypertension, and thyroid function.

²Adjusted for age, gender, smoking, and thyroid function.

³Adjusted for age, gender, smoking, and hypertension.

SNP: Single nucleotide polymorphism; CVC: Cross-validation consistency.

Table 12 Analysis of interaction between rs820196 genotype and smoking in patients with heart rate variability ≥ 30% and < 30%

Smoking	rs820196 genotype	HRV ≥ 30% (n = 22)	HRV < 30% (n = 170)	OR (95%CI)	P value
No	TT	6 (7.89)	70 (92.11)	1.00 (Reference)	-
Yes	TT	1 (9.09)	10 (90.91)	1.47 (0.15, 14.27)	0.74
No	TC	13 (19.70)	53 (80.30)	2.91 (1.03, 8.20)	0.04^a
Yes	TC	1 (5.26)	18 (94.74)	0.80 (0.088, 7.36)	0.85
No	CC	1 (5.88)	16 (94.12)	0.81 (0.089, 7.35)	0.85
Other		0 (0.00)	3 (100.00)	-	-

^aP < 0.05 vs nonsmokers with the rs820196 TT.

Logistic regression analyses adjusting for age, gender, hypertension, and thyroid function. HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval.

Table 13 Best single nucleotide polymorphism-single nucleotide polymorphism interaction models identified by generalized multifactor dimensionality reduction with covariable adjustment (heart rate variability cutoff value = 15%)

Best model	Training balanced accuracy	Testing balanced accuracy	CVC	P value
rs820196	0.5885	0.5920	10/10	0.039^a
rs820196, rs1713449	0.6301	0.5798	9/10	0.052
rs938886, rs820196, rs1713449	0.6335	0.5885	10/10	0.066

^aP < 0.05 means the one-locus model of RecQ like helicase 5 rs820196 is the best model for predicting heart rate variability risk.

Adjusted for age, gender, hypertension, smoking, and thyroid function. CVC: Cross-validation consistency.

Table 14 Association analysis of interactions between different genotypes of single nucleotide polymorphism loci and risk of heart rate variability ≥ 15%

SNPs genotypes			HRV ≥ 15% (n = 72)	HRV < 15% (n = 120)	OR (95%CI)	P value
rs820196 rs1713449
TT	CC		12 (27.27)	32 (72.73)	1.00 (Reference)	-
TT	CT		10 (27.78)	26 (72.22)	1.03 (0.38, 2.79)	0.95
TT	TT		5 (71.43)	2 (28.57)	6.87(1.15, 41.09)	0.04^a
TC	CC		15 (42.86)	20 (57.14)	2.07 (0.79, 5.45)	0.14
TC	CT		22 (55.00)	18 (45.00)	3.26 (1.30, 8.20)	0.01^b
TC	TT		3 (30.00)	7 (70.00)	1.06 (0.22, 5.06)	0.94
CC	CC		2 (20.00)	8 (80.00)	0.56 (0.098, 3.21)	0.52
CC	CT		2 (25.00)	6 (75.00)	0.87 (0.15, 5.11)	0.88
CC	TT		1 (50.00)	1 (50.00)	2.90 (0.17, 50.84)	0.47
rs938886 rs1713449 rs820196
GG	CC	TT	12 (27.27)	32 (72.73)	1.00 (Reference)
GG	CC	TC	15 (42.86)	20 (57.14)	1.87 (0.74, 4.77)	0.19
GG	CC	CC	2 (20.00)	8 (80.00)	0.51 (0.09, 2.87)	0.45
GC	CT	TT	10 (27.78)	26 (72.22)	0.93 (0.36, 2.44)	0.89
GC	CT	TC	22 (55.00)	18 (45.00)	2.96 (1.21, 7.22)	0.02^c
GC	CT	CC	2 (25.00)	6 (75.00)	0.79 (0.14, 4.57)	0.79
CC	TT	TT	4 (80.00)	1 (20.00)	9.71 (0.97, 96.94)	0.05
CC	TT	TC	3 (30.00)	7 (70.00)	0.98 (0.21, 4.63)	0.98
Others			2 (50.0)	2 (50.0)	-	-

^aP < 0.05 vs TT-CC.

^bP < 0.05 vs TT-CC.

^cP < 0.05 vs GG-CC-TT. Logistic regression analyses adjusting for age, gender, smoking, hypertension, and thyroid function.

SNPs: Single nucleotide polymorphisms; HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval.

Table 15 Single nucleotide polymorphism-smoking, single nucleotide polymorphism-hypertension and SNP-thyroid function interaction models in patients with heart rate variability ≥ 15% evaluated with the generalized multifactor dimensionality reduction approach

Best model	Training balanced accuracy	Testing balanced accuracy	CVC	P value
SNP-smoking interaction¹
Smoking	0.5191	0.5171	10/10	0.349
rs820196-smoking	0.6148	0.5954	10/10	0.022^a
rs820196-rs1713449-smoking	0.6510	0.5764	9/10	0.065
SNP-hypertension interaction²
Hypertension	0.5156	0.3564	10/10	0.995
rs820196-hypertension	0.5885	0.5920	10/10	0.043^b
rs820196-rs1713449-hypertension	0.6434	0.5343	9/10	0.219
SNP-thyroid function interaction³
Thyroid function	0.5126	0.5113	10/10	0.381
rs820196-thyroid function	0.5888	0.5814	10/10	0.065
rs820196-rs1713449-thyroid function	0.6411	0.5706	9/10	0.075

^aP < 0.05 means rs820196-smoking two-factor model associated with Heart rate variability (HRV) ≥ 15%.

^bP < 0.05 means rs820196-hypertension two-factor model associated with HRV ≥ 15%.

¹Adjusted for age, gender, hypertension, and thyroid function.

²Adjusted for age, gender, smoking, and thyroid function.

³Adjusted for age, gender, smoking, and hypertension.

SNP: Single nucleotide polymorphism; CVC: Cross-validation consistency.

Table 16 Analysis of interaction between rs820196 genotype and smoking and hypertension in patients with heart rate variability ≥ 15% and < 15%

Environment	rs820196 genotype	HRV ≥ 15% (n = 72)	HRV < 15% (n = 120)	OR (95%CI)	P value
Smoking
No	TT	22 (28.95)	54 (71.05)	1.00 (Reference)	-
Yes	TT	5 (45.45)	6 (54.55)	2.12 (0.57, 7.95)	0.26
No	TC	33 (50.00)	33 (50.00)	2.53 (1.26, 5.08)	0.01^a
Yes	TC	7 (36.84)	12 (63.16)	1.43 (0.48, 4.22)	0.52
No	CC	3 (17.65)	14 (82.35)	0.48 (0.12, 1.89)	0.30
Yes	CC	2 (66.67)	1 (33.33)	4.68 (0.39, 56.33)	0.22
Hypertension
No	TT	18 (32.73)	37 (67.27)	1.00 (Reference)	-
Yes	TT	9 (28.13)	23 (71.88)	0.77 (0.28, 2.11)	0.62
No	TC	25 (46.30)	29 (53.70)	1.75 (0.80, 3.82)	0.16
Yes	TC	15 (48.39)	16 (51.61)	1.90 (0.75, 4.78)	0.18
No	CC	3 (23.08)	10 (76.92)	0.58 (0.14, 2.42)	0.45
Yes	CC	2 (28.57)	5 (71.43)	0.72 (0.12, 4.26)	0.72

^aP < 0.05 vs nonsmokers with the rs820196 TT.

Logistic regression analyses adjusting for age, gender, and thyroid function. HRV: Heart rate variability; OR: Odds ratio; CI: Confidence interval.

Citation: Yao S, Yuan Y, Zhang J, Yu Y, Luo GH. Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy. World J Gastrointest Surg 2023; 15(10): 2154-2170
URL: https://www.wjgnet.com/1948-9366/full/v15/i10/2154.htm
DOI: https://dx.doi.org/10.4240/wjgs.v15.i10.2154