Genetic Association of rs10757278 on Chromosome 9p21 and Coronary Artery Disease in a Saudi Population

Figures & data

Figure 1 The rs10757278 genotyping for the G/A alleles using ARMS-PCR. Lane 1: 50 bp ladder. Lane 2–6: GG genotypes. Lane 7–11: AA genotypes. Lane 12–20: AG genotypes.

Figure 2 Representation of the validation by DNA sequencing for rs10757278.

Table 1 Characteristics of the Study Population Cases and Controls

Variables	Cases (n=437)	Controls (n=251)	P
Age (Years)	59.04 (5.19)	57.94 (5)	0.08
Weight (Kg)	88.85 (9.92)	76.96 (11.25)	0.000
BMI (Kg/m^2)	29.63 (3.08)	18.91 (3.09)	0.000
Systolic BP (mmHg)	142.85 (9.92)	118.97 (9.21)	0.000
Diastolic BP (mmHg)	84.94 (3.97)	78.98 (6.14)	0.000
Blood glucose (mg/dl)	163.84 (10.91)	111.97 (10.23)	0.000
TC (mg/dl)	242.03 (7.35)	171.87 (5.34)	0.000
HDL-c (mg/dl)	39.1 (3.14)	58.27 (4.39)	0.000
LDL-c (mg/dl)	173.04 (4.87)	120.89 (3.86)	0.000
TG (mg/dl) *	223.18 (7.04)	142.42 (5.34)	0.000*
Gender (male%)	289 (66.1)	114 (45.4)	0.055
BMI group: Normal	114 (26.1)	105 (41.9)	0.000
Overweight	143 (32.7)	69 (27.5)
Obese	180 (41.2)	77 (30.6)
Smoking	203 (46.5)	69 (27.5)	0.000
Exercise	107 (24.5)	72 (28.5)	0.132
Diabetes	252 (57.7)	42 (16.7)	0.000
Hypertension	297 (68)	54 (21.5)	0.000
Event: Stroke	109 (24.9)	9 (3.6)	0.000
Heart failure	30 (6.9)	6 (2.4)	0.007
CABG	36 (8.2)	–	–

Notes: Continuous variables are presented as [mean (SD)] → compared by a Student’s t-test. Nominal variables are presented as frequency, No. (%) → compared by a Pearson’s chi square test. *Median (SEM) → Mann–Whitney U-test.

Abbreviations: BMI, body mass index; TC, total cholesterol; TG, triglycerides. HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; CABG, coronary artery bypass graft.

Table 2 Comparison of the Different Mode of Inheritance of the Genotypes and Allele Frequencies with the rs10757278 Polymorphism in CAD Cases and Control Subjects

Genotype	Case (437)		Control (251)		OR	95% CI	p
	No.	%	No.	%
AA	95	21.7	73	29.1	1		Reference
AG	214	49	132	52.6	1.246	0.856–1.811	0.250
GG	128	29.3	46	18.3	2.138	1.357–3.369	0.0009
Dominant (AA vs AG + GG)
	95	21.7	73	29.1	0.6773	0.475–0.965	0.030
Co-dominant (AG vs GG+AA)
	214	49	132	52.6	0.8651	0.6341–1.18	0.360
Recessive (GG vs AG+AA)
	128	29.3	46	18.3	1.846	1.262–2.7	0.001
Alleles
A	404	46.2	278	55.4	1		Reference
G	470	53.8	224	44.6	1.444	1.158–1.8	0.001

Note: OR, odds ratio by Pearson’s chi square test.

Figure 3 Genotype and allele frequencies of the CAD cases and control subjects.

Table 3 Risk Factor Distribution Across Genotypes

No.	AA (n=95)	AG (n=214)	GG (n=128)	p
Age	58.62 (5.36)	59.17 (4.89)	59.14 (5.58)	0.668
Weight (Kg)	87.09 (9.36)	88.97 (10.26)	89.95 (9.61)	0.101
BMI (Kg/m^2)	29.89 (3.04)	29.52 (3.22)	29.63 (2.89)	0.629
Systolic BP (mmHg)	144.58 (10.57)	142.65 (10.18)	141.89 (8.81)	0.124
Diastolic BP (mmHg)	85.63 (4.23)	84.86 (4.07)	84.56 (3.53)	0.124
Blood glucose (mg/dl)	161.48 (10.85)	163.81 (10.73)	167.40 (11.31)	0.07
TC (mg/dl)	242.28 (7.64)	242.12 (7.61)	242.71 (6.69)	0.827
LDL-c (mg/dl)	172.66 (4.96)	172.82 (4.94)	173.69 (4.67)	0.190
HDL-c (mg/dl)	39.11 (3.01)	39.25 (3.27)	39.86 (3.03)	0.827
TG (mg/dl) *	223.53 (6.6)	222.81 (7.16)	223.53 (7.2)	0.573*
Gender (male%)	67 (70.53)	138 (64.49)	84 (65.63)	0.579
BMI group:
Normal	30 (31.58)	54 (25.23)	30 (23.44)	0.149
Overweight	29 (30.53)	79 (36.92)	35 (27.34)	–
Obese	36 (37.89)	81 (37.85)	63 (49.23)	–
Smoking	46 (48.42)	104 (48.60)	53 (41.42)	0.396
Exercise	35 (36.84)	42 (19.63)	30 (23.44)**	0.005
Hypertension	56 (58.95)	146 (68.22)	95 (74.23)	0.054
Diabetes	39 (41.05)	136 (63.55)	77 (60.16)**	0.001
History of:
Stroke	31 (32.63)	53 (24.77)	25 (19.53)	0.082
Heart failure	5 (5.26)	16 (7.48)	9 (7.03)	0.774
CABG	9 (9.47)	19 (8.88)	8 (6.25)	0.613

Notes: Continuous variables are presented as [mean (SD)] → ANOVA test. Nominal variables are presented as frequency, No. (%) → Pearson’s chi square test. *Median (SEM) → Kruskal–Wallis test. **Post Hoc test.

Abbreviations: BMI, body mass index; TC, total cholesterol; TG, triglycerides. HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; CABG, coronary artery bypass graft.

Table 4 Multiple Regression Analysis of the Associated Risk Factors

Variable	Unstandardized Coefficients		Standardized Coefficients	t	p
	B	SE	ß
GG genotype	0.619	0.09	0.33	4.81	0.005
TC	0.071	0.066	1.92	3.15	0.000
LDL-c	0.013	0.011	0.22	2.67	0.008
TG	0.025	0.006	1.89	5.12	0.000
BMI	0.618	0.12	0.18	3.06	0.03
DM	0.432	0.14	0.38	4.16	0.000
HTN	0.638	0.13	0.19	2.94	0.000
Physical activity	−0.271	0.11	0.09	1.82	0.323

Abbreviations: BMI, body mass index; TC, total cholesterol TG, triglycerides; LDL-c, low-density lipoprotein cholesterol; DM, diabetes mellitus; HTN, hypertension.