Variants in CDHR3, CACNAC1, and LTA Genes Predisposing Sensitivity and Response to Warfarin in Patients with Cardiovascular Disease

Figures & data

Table 1 Genes and SNPs Characteristics

Gene	SNP	Chr. Position*	Alleles	Variant Type
CDHR3	rs10270308	7:106030821	T/C	Synonymous
CACNAC1	rs216013	12:2620466	A/G	Intron
LTA	rs1041981	6:31573007	C/A	Missense

Note: *From NCBI Human Genome Assembly Build.

Table 2 Association of CDHR3, CACNAC1, and LTA SNPs with Warfarin Sensitivity During the Initiation Phase of Treatment with Warfarin in Cardiovascular Patients (n=212)

Gene	SNP	Genotype	Sensitive	Moderate	Resistance	Overall P-value*
CDHR3	rs10270308	CT	(2/14) 14.3%	(10/14) 71.4%	(2/14) 14.3%	1
		P-value	0.99	0.98	0.99
		TT	(30/196) 15.3%	(135/196) 68.9%	(31/196) 15.8%
		P-value	0.99	0.98	0.99
CACNAC1	rs216013	AA	(22/120) 18.3%	(77/120) 64.2%	(2/120) 17.5%	0.243
		P-value	0.14	0.10	0.53
		AG	(9/79) 11.4%	(57/79) 72.2%	(13/79) 16.5%
		P-value	0.24	0.41	0.08
		GG	(1/12) 8.3%	(11/12) 91.7%	(0/12) 0.0%
		P-value	0.53	0.92	0.12
LTA	rs1041981	AA	(2/20) 10%	(13/20) 65%	(5/20) 25%	0.05
		P-value	0.50	0.69	0.25
		CA	(18/106) 17%	(79/106) 74.5%	(9/106) 8.5%
		P-value	0.44	0.08	0.003
		CC	(12/86) 14%	(54/86) 62.8%	(20/86) 23.3%
		P-value	0.70	0.11	0.02

Note: *P value <0.05 is considered significant.

Table 3 Association of CDHR3, CACNAC1, and LTA SNPs with Warfarin Sensitivity During the Stabilization Phase of Treatment with Warfarin in Cardiovascular Patients (n=139)

Gene	SNP	Genotype	Sensitive	Moderate	Resistance	Overall P-value*
CDHR3	rs10270308	CT	(0/9) 0.0%	(7/9) 77.8%	(2/9) 22.2%	0.427
		P-value	0.19	0.32	0.92
		TT	(20/128) 15.6%	(77/128) 60.2%	(31/128) 24.2%
		P-value	0.19	0.32	0.92
CACNAC1	rs216013	AA	(11/77) 14.3%	(47/77) 61%	(19/77) 24.7%	0.117
		P-value	0.92	0.84	0.84
		AG	(6/55) 10.9%	(35/55) 63.6%	(14/55) 25.5%
		P-value	0.32	0.69	0.76
		GG	(3/6) 50%	(3/6) 50%	(0/6) 0.0%
		P-value	0.01	0.55	0.16
LTA	rs1041981	AA	(2/17) 11.8%	(9/17) 52.9%	(6/17) 35.3%	0.312
		P-value	0.76	0.42	0.23
		CA	(11/69) 15.9%	(47/69) 68.1%	(11/69) 15.9%
		P-value	0.62	0.13	0.04
		CC	(7/53) 13.2%	(30/53) 56.6%	(16/53) 30.2%
		P-value	0.76	0.32	0.16

Note: *P value <0.05 is considered significant.

Table 4 Association of CDHR3, CACNAC1, and LTA SNPs with Variability on Warfarin Required Doses

Gene	SNP	Genotype	Initiation Dose	Overall P-value*	Maintenance Dose	Overall P-value*
CDHR3	rs10270308	CT	37.65 [11.15]	0.945	38.43 [18.17]	0.515
		TT	38.09 [23.77]		42.48 [14.81]
CACNAC1	rs216013	AA	39.13 [28.79]	0.593	38.68 [18.71]	0.173
		AG	37.51 [12.31]		40.01 [17.01]
		GG	32.27 [9.79]		25.67 [9.74]
LTA	rs1041981	AA	41.67 [15.69]	0.506	43.20 [22.51]	0.006
		CA	36.32 [28.07]		33.74 [12.08]
		CC	39.37 [16.87]		43.64 [16.99]

Notes: *P value <0.05 is considered significant. Mean standard deviation in square brackets.

Table 5 Post Hoc Tests for the Association of CDHR3, CACNAC1, and LTA SNPs with Variability on Warfarin Required Doses

Gene	SNP	Genotype		Initiation Dose P-value*	Maintenance Dose P-value*
CACNAC1	rs216013	AA	AG	0.88	0.89
			GG	0.59	0.19
		AG	AA	0.88	0.89
			GG	0.75	0.15
		GG	AA	0.59	0.19
			AG	0.75	0.15
LTA	rs1041981	AA	CA	0.61	0.09
			CC	0.92	0.96
		CA	AA	0.61	0.09
			CC	0.63	0.009
		CC	AA	0.92	0.96
			CA	0.63	0.009

Notes: *P value <0.05 is considered significant. Compare the means of initiation and maintenance dose among all genotypes. Post hoc are not performed for rs10270308 because it is fewer than three groups.