Association between CBS gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region and coronary artery disease: a meta-analysis

Figures & data

Figure 1. Flow chart of study selection.

Table 1. Characteristics of the included studies in the meta-analysis.

	First-author	Year	Country	Ethnicity	Sources of Controls	Diagnosis methods	Coronary artery disease group			Control group
							Disease	Number of cases	HWE balance test	Crowd characteristics	Number of cases	HWE balance test
T833C	Dilley^Citation17	2001	United States	North American	HCC	unclear	MI	107	unclear	healthy	172	unclear
	Xu Haiyan^Citation18	1999	China	Asian	HCC	CAA	CAD	209	unclear	healthy	101	unclear
	Chen Xin^Citation20	2003	China	Asian	HCC	Criteria for CAD	CAD	107	unclear	healthy	96	unclear
	Chen Yulan^Citation26	2006	China	Asian	HCC	CAA	CAD	189	Yes	healthy	131	Yes
G919A	Li Lifan^Citation27	2005	China	Asian	HCC	Criteria for CAD	CAD	65	unclear	healthy	65	unclear
	Xu Haiyan^Citation19	2007	China	Asian	HCC	CAA	MI or CAD	255	unclear	healthy	170	unclear
	Chen Xin^Citation20	2003	China	Asian	HCC	Criteria for CAD	CAD	107	unclear	healthy	96	unclear
844ins68	Iqbal^Citation21	2016	Karachi Pakistan	Asian	PCC	Criteria for AMI	AMI	143	No	healthy	154	No
	Zhang^Citation22	2001	China	Asian	HCC	CAA	MI	73	unclear	healthy	100	unclear
	Yang Linyan^Citation28	2011	China	Asian	HCC	Criteria for CAD	CAD	210	Yes	healthy	249	Yes
	Luo Dan^Citation29	2009	China	Asian	HCC	CAA	DM2+CAD	104	unclear	healthy	91	unclear
	Li Yaohuang^Citation30	2005	China	Asian	HCC	Crieria for CAD	CAD	86	unclear	healthy	143	unclear
	Jiao Kunli^Citation31	2006	China	Asian	HCC	CAA	MI	208	Yes	healthy	500	Yes
	He Guanjun^Citation32	2015	China	Asian	HCC	CAA	CAD	260	unclear	healthy	300	unclear

PCC: population-based case-control study; HCC: hospital-based case-control study; CAA: coronary angiography; Criteria for CAD: diagnosis of coronary heart disease; MI: myocardial infarction; AMI: acute myocardial infarction; T2DM: type 2 diabetes.

Table 2. NOS quality evaluation form.

	Inclusion study	Study population selection				Group-to-group	comparison of exposure factors			Total (minutes)
		①	②	③	④	⑤	⑥	⑦	⑧
T833C	Dilley 2001^Citation17	1	1	1	1	2	1	1	0	8
	Xu Haiyan 1999^Citation18	1	1	1	1	2	1	1	1	9
	Chen Xin 2003^Citation20	1	1	1	1	1	1	1	1	8
	Chen Yulan 2006^Citation26	1	1	1	1	2	1	1	1	9
G919A	Li Lifan 2005^Citation27	1	1	1	1	1	1	1	1	8
	Xu Haiyan 2007^Citation19	1	1	1	1	2	1	1	0	8
	Chen Xin 2003^Citation20	1	1	1	1	1	1	1	1	8
844ins68	Iqbal 2016^Citation21	1	1	1	1	2	1	1	1	9
	Zhang 2001^Citation22	1	1	1	1	1	1	1	1	8
	Yang Linyan 2011^Citation28	1	1	1	1	0	1	1	1	7
	Luo Dan 2009^Citation29	1	1	1	1	1	1	1	1	8
	Li Yaohuang2005^Citation30	1	1	1	1	1	1	1	1	8
	Jiao Kunli 2006^Citation31	1	1	1	1	2	1	1	1	9
	He Guanjun 2015^Citation32	1	1	1	1	2	1	1	1	9

①The case definition is adequate with independent validation ② Consecutive or obviously representative series of cases ③ Community controls ④ Controls with no history of disease (endpoint) ⑤ Cases and controls with comparable ages and comparability on any other factors ⑥ Ascertainment of exposure using secure records (eg surgical records) or structured interviews with blinding to case/control ⑦ Ascertainment of exposure using the same method for cases and controls ⑧ Ascertainment of exposure with non-response rate for both groups.

Table 3. Distributions of the genotypes of the CBS T833C、G919A、844ins68.

		Cases			Controls
	Inclusion study	CC(%)	CT(%)	TT(%)	CC(%)	CT(%)	TT(%)
CBS T833C	Dilley 2001^[17]	7(6.54)	36(33.65)	64(59.81)	8(4.65)	56(32.56)	108(62.79)
	Xu Haiyan 1999^[18]	21(10.04)	94(44.98)	94(44.98)	2(1.98)	28(27.72)	71(70.30)
	Chen Xin 2003^[20]	9(8.41)	26(24.30)	72(67.29)	2(2.08)	9(9.38)	85(88.54)
	Chen Yulan 2006^[26]	27(14.29)	52(27.51)	110(58.20)	16(12.21)	31(23.66)	84(64.12)
		GG(%)	AG(%)	AA(%)	GG(%)	AG(%)	AA(%)
CBS G919A	Li Lifan 2005^[27]	40(61.54)	19(29.23)	6(9.32)	53(81.54)	10(15.38)	2(3.08)
	Xu Haiyan 2007^[19]	19(7.45)	202(79.22)	34(13.33)	5(2.94)	147(86.47)	18(10.59)
	Chen Xin 2003^[20]	79(73.83)	22(20.56)	6(5.61)	85(88.54)	9(9.38)	2(2.08)
		DD(%)	ID(%)	II(%)	DD(%)	ID(%)	II(%)
CBS 844ins68	Iqbal 2016^[21]	127(88.81)	14(9.79)	2(1.40)	132(85.71)	21(13.64)	1(0.65)
	Zhang 2001^[22]	72(98.63)	1(1.37)	0	95(95.00)	5(5.00)	0
	Yang Linyan 2011^[28]	185(88.10)	24(11.43)	1(0.47)	217(87.15)	30(12.05)	2(0.80)
	Luo Dan 2009^[29]	102(98.07)	2(1.92)	0	85(93.41)	6(6.59)	0
	Li Yaohuang2005^[30]	67(77.91)	16(18.60)	3(3.48)	112(78.32)	27(18.88)	4(2.80)
	Jiao Kunli 2006^[31]	184(88.46)	23(11.06)	1(0.48)	463(92.60)	35(7.00)	2(0.40)
	He Guanjun 2015^[32]	235(90.38)	20(7.69)	5(1.92)	278(92.67)	16(5.33)	6(2.00)

Table 4. Summary of odds ratios (95% CI) in the analysis of the association between the CBS polymorphism and CAD susceptibility in different models.

Polymorphism	Model	Test of association		Test of heterogeneity		Forest plot
		OR (95% CI)	P value	I^2	P
T833C	Homozygote model (CC vs. TT)	2.46(1.04 ~ 5.83)	0.04	57%	0.07	Figure S2-1
	Dominant model (CC+CT vs. TT)	1.92(1.11 ~ 3.32)	0.02	76%	0.006	Figure S2–2
	Recessive model (CC vs. CT+TT)	1.88(1.17 ~ 3.03)	0.01	42%	0.16	Figure S2–3
G919A	Homozygote model (AA vs. GG)	1.66(0.40 ~ 6.92)	0.48	65%	0.06	Figure S2–4
	Dominant model (AA+AG vs. GG)	1.48(0.45 ~ 4.82)	0.52	83%	0.003	Figure S2–5
	Recessive model (AA vs. AG+GG)	1.58(0.93 ~ 2.70)	0.09	0%	0.45	Figure S2–6
844ins68	Homozygote model (II vs. DD)	1.10(0.51 ~ 2.39)	0.81	0%	0.96	Figure S2–7
	Dominant model (II+ID vs. DD)	1.04(0.80 ~ 1.35)	0.76	29%	0.21	Figure S2–8
	Recessive model (II vs. ID+DD)	1.09(0.51 ~ 2.36)	0.82	0%	0.96	Figure S2–9

OR – odds ratio; CI – confidence interval.

Table 5. Meta-analysis of the association between CBS T833C polymorphism and risk of CAD.

Indexes		No. of studies	Homozygote model (CC vs. TT)			Dominant model (CC+CT vs. TT)			Recessive model (CC vs. CT+TT)
			OR	95%CI	p value	OR	95%CI	p value	OR	95%CI	p value
Sample size	Large(>250)	3	1.93	(1.16，3.21)	0.01	1.6	(1.21，2.10)	0.0009	1.69	(1.02，2.79)	0.04
	Small(≤250)	1	5.31	(1.11，25.38)	0.04	3.76	(1.78，7.93)	0.0005	4.32	(0.91，20.50)	0.07
Diagnosis methods	CAA	2	2.08	(1.16,3.73)	0.01	1.86	(1.33,2.61)	0.0003	1.76	(0.99,3.15)	0.06
	Others	2	2.39	(1.04,5.52)	0.04	1.68	(1.13,2.51)	0.01	2.16	(0.94,4.97)	0.07
Ethnicity	Chinese	3	2.38	(1.38,4.10)	0.002	2.12	(1.56,2.87)	<0.00001	2	(1.17,3.43)	0.01
	American	1	1.48	(0.51，4.26)	0.47	1.13	(0.69，1.86)	0.62	1.44	(0.50，4.08)	0.5

Table 6. The effect of publication bias was assessed by Begg’s and Egger’s linear regression tests.

Polymorphism	Model	Test of Begg(P value)	Test of Egger(P value)		Figure
T833C	Homozygote model (CC vs. TT)	0.308	0.091	FIG.S3-A
	Dominant model (CC+CT vs. TT)	0.734	0.311	FIG.S3-B
	Recessive model(CC vs. CT+TT)	0.308	0.069	FIG.S3-C
G919A	Homozygote model (AA vs. GG)	0.296	0.027	FIG.S3-D
	Dominant model (AA+AG vs. GG)	0.296	0.118	FIG.S3-E
	Recessive model (AA vs. AG+GG)	0.296	0.054	FIG.S3-F
844ins68	Homozygote model (II vs. DD)	0.826	0.779	FIG.S3-G
	Dominant model (II+ID vs. DD)	0.035	0.031	FIG.S3-H
	Recessive model (II vs. ID+DD)	0.806	0.747	FIG.S3-I

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