PFKP and GPC6 Variants Were Correlated with Alcohol-Induced Femoral Head Necrosis Risk in the Chinese Han Population

Figures & data

Table 1 Demographic and Clinical Data of Alcohol-Induced ONFH Cases and Healthy Controls

Variables	Case (N = 201)	Control (N = 201)	P-value
Age (Mean ± SD)	42.68 ± 12.88	42.87 ± 13.27	0.888
Clinical indexes (Mean ± SD)
TC (mmol/L)	4.65 ± 0.92	4.54 ± 0.80	0.250
TG (mmol/L)	1.89 ± 1.28	2.01 ± 1.32	0.401
HDL-C (mmol/L)	1.04 ± 0.24	1.09 ± 0.20	0.054
LDL-C (mmol/L)	2.73 ± 0.85	2.65 ± 0.70	0.394
ApoA1 (g/L)	1.22 ± 0.22	1.26 ± 0.14	0.514
ApoB (g/L)	1.62 ± 8.75	1.07 ± 0.20	0.821
Clinical characteristics (N %)
Hip lesions
Unilateral	44 (21.9%)
Bilateral	157 (78.1%)
Clinical stage
I + II	54 (26.9%)
III + IV	147 (73.1%)

Note: P-value was calculated by independent samples t-test.

Abbreviations: SD, standard deviation; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; ApoA, Apolipoproteins A; ApoB, Apolipoproteins B.

Table 2 The Information of Selected Variants in PFKP and GPC6 Genes

SNP-ID	Gene	Chr	Position	Allele		MAF		HWE p-value
				Ref	Alt	Case	Control
rs35863365	PFKP	10	Intron	C	T	0.149	0.139	0.234
rs8181285	PFKP	10	Intron	A	G	0.348	0.393	0.760
rs10903966	PFKP	10	Intron	T	C	0.557	0.490	1.000
rs11251720	PFKP	10	Intron	T	C	0.067	0.060	0.518
rs4773724	GPC6	13	Intron	T	G	0.359	0.405	0.107
rs1008993	GPC6	13	Intron	C	T	0.162	0.142	0.036
rs9523981	GPC6	13	Intron	C	T	0.384	0.346	0.275
rs7320969	GPC6	13	Intron	G	C	0.318	0.341	0.059
rs59624626	GPC6	13	Intron	T	G	0.304	0.289	0.864

Note: HWE p-value was calculated by Pearson chi-square test.

Abbreviations: SNP, single nucleotide polymorphism; Chr, chromosome; Ref, reference; Alt, alteration; MAF, minor allele frequency; HWE, Hardy-Weinberg equilibrium.

Table 3 Association Analysis of PFKP and GPC6 Polymorphisms with Alcohol-Induced ONFH Susceptibility in Genetic Models

Gene	SNP-ID	Model	Genotype	Frequency		Without Adjustment		With Adjustment
				Case	Control	OR (95% CI)	p^a-value	OR (95% CI)	p^b-value
PFKP	rs10903966	Codominant	C/C	68	48	1		1
			T/C	80	101	0.90 (0.55–1.47)	0.661	0.90 (0.55–1.47)	0.667
			T/T	46	52	1.60 (0.93–2.75)	0.089	1.61 (0.94–2.77)	0.086
		Dominant	C/C	68	48	1		1
			T/C-T/T	126	153	1.12 (0.71–1.77)	0.620	1.13 (0.71–1.78)	0.613
		Recessive	C/C-T/C	148	149	1		1
			T/T	46	52	1.72 (1.11–2.67)	0.015	1.73 (1.11–2.68)	0.015
		Log-additive	–	–	–	1.28 (0.98–1.68)	0.072	1.29 (0.98–1.69)	0.070
GPC6	rs7320969	Codominant	C/C	24	17	1		1
			G/C	80	103	0.65 (0.43–0.98)	0.041	0.65 (0.43–0.98)	0.041
			G/G	97	81	1.18 (0.59–2.35)	0.639	1.18 (0.59–2.35)	0.639
		Dominant	C/C	24	17	1		1
			G/C-G/G	177	184	0.72 (0.49–1.07)	0.109	0.72 (0.49–1.08)	0.109
		Recessive	C/C-G/C	104	120	1		1
			G/G	97	81	1.47 (0.76–2.82)	0.251	1.47 (0.76–2.82)	0.251
		Log-additive	–	–	–	0.90 (0.67–1.22)	0.493	0.90 (0.67–1.22)	0.494

Notes: p^a-value was calculated by logistic regression analysis without adjustment. p^b-value was calculated by logistic regression analysis adjusted for gender and age. Bold indicates that the SNP is statistical significance (p < 0.05).

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 4 FPRP Analysis for the Significant Associations of ARRDC3 SNPs with Glioma Risk

Model	OR(95% CI)	Power	Prior Probability
			0.25	0.1	0.01	0.001	0.0001
PFKP rs10903966
C/C-T/C vs T/T	1.73 (1.11–2.68)	0.742	0.054	0.146	0.653	0.950	0.995
GPC6 rs7320969
C/C vs G/C	0.65 (0.43–0.98)	0.895	0.118	0.286	0.815	0.978	0.998

Note: Noteworthiness at the 0.2 level of FPRP.

Table 5 Association Analysis Between GPC6 Polymorphisms and Alcohol-Induced ONFH Susceptibility in ≤42 Years Group

SNP-ID	Model	Genotype	Frequency		With Adjustment
			Case	Control	OR (95% CI)	p^b-value
rs4773724	Allele	G	65	85	1
		T	129	111	0.66 (0.44–0.99)	0.045
	Codominant	G/G	13	15	1
		T/G	39	55	0.44 (0.24–0.82)	0.010
		T/T	45	28	0.54 (0.22–1.30)	0.168
	Dominant	G/G	13	15	1
		T/G-T/T	84	83	0.46 (0.26–0.84)	0.011
	Recessive	G/G-T/G	52	70	1
		T/T	45	28	0.86 (0.38–1.91)	0.704
	Log-additive	–	–	–	0.65 (0.43–0.99)	0.045
rs9523981	Allele	T	80	65	1
		C	118	133	1.39 (0.92–2.09)	0.118
	Codominant	T/T	18	6	1
		T/C	44	53	0.90 (0.49–1.64)	0.701
		C/C	37	40	3.23 (1.15–9.03)	0.026
	Dominant	T/T	18	6	1
		T/C-C/C	81	93	1.13 (0.64–2.02)	0.671
	Recessive	T/T-T/C	62	59	1
		C/C	37	40	3.44 (1.30–9.09)	0.013
	Log-additive	–	–	–	1.42 (0.92–2.18)	0.110

Notes: p^a-value was calculated by logistic regression analysis without adjustment. p^b-value was calculated by logistic regression analysis adjusted for gender and age. Bold indicates that the SNP is statistical significance (p < 0.05).

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 6 Association Analysis Between PFKP and GPC6 Polymorphisms and Alcohol-Induced ONFH Susceptibility After Necrotic Site Stratification Analysis

SNP-ID	Model	Genotype	Frequency		Without Adjustment		With Adjustment
			Case	Control	OR (95% CI)	p^a-value	OR (95% CI)	p^b-value
Unilateral necrotic site
rs7320969	Codominant	C/C	8	17	1		1
		G/C	12	103	0.39 (0.19–0.83)	0.015	0.39 (0.19–0.84)	0.015
		G/G	24	81	1.59 (0.61–4.13)	0.343	1.59 (0.61–4.12)	0.346
	Dominant	C/C	8	17	1	–	1	–
		G/C-G/G	36	184	0.56 (0.29–1.09)	0.086	0.56 (0.29–1.09)	0.087
	Recessive	C/C-G/C	20	120	1	–	1	–
		G/G	24	81	2.41 (0.97–5.99)	0.060	2.39 (0.96–5.97)	0.061
	Log-additive	–	–	–	0.90 (0.54–1.49)	0.677	0.90 (0.54–1.49)	0.676
Bilateral necrotic sites
rs10903966	Codominant	C/C	54	48	1		1
		T/C	66	101	1.10 (0.64–1.89)	0.740	1.10 (0.64–1.89)	0.735
		T/T	31	52	1.89 (1.05–3.41)	0.035	1.89 (1.05–3.42)	0.035
	Dominant	C/C	54	48	1		1
		T/C-T/T	97	153	1.35 (0.81–2.24)	0.244	1.35 (0.82–2.25)	0.241
	Recessive	C/C-T/C	120	149	1		1
		T/T	31	52	1.77 (1.12–2.82)	0.016	1.78 (1.12–2.83)	0.015
	Log-additive	–	–	–	1.40 (1.04–1.88)	0.028	1.40 (1.04–1.88)	0.027
rs9523981	Codominant	T/T	28	20	1		1
		T/C	71	99	1.03 (0.65–1.63)	0.893	1.03 (0.66–1.63)	0.889
		C/C	57	82	2.01 (1.04–3.92)	0.039	2.02 (1.04–3.93)	0.039
	Dominant	T/T	28	20	1		1
		T/C-C/C	128	181	1.20 (0.78–1.84)	0.413	1.20 (0.78–1.84)	0.410
	Recessive	T/T-T/C	99	119	1		1
		C/C	57	82	1.98 (1.07–3.67)	0.030	1.98 (1.07–3.67)	0.030
	Log-additive	–	–	–	1.31 (0.96–1.78)	0.091	1.31 (0.96–1.78)	0.090

Notes: p^a-value was calculated by logistic regression analysis without adjustment. p^b-value was calculated by logistic regression analysis adjusted for gender and age. Bold indicates that the SNP is statistical significance (p < 0.05).

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Figure 1 Haplotype block map of PFKP variants. The numbers inside the diamonds indicate the D′ for pairwise analyses.

Figure 2 Haplotype block map of GPC6 variants. The numbers inside the diamonds indicate the D′ for pairwise analyses.

Figure 3 Multifactor dimensionality reduction (MDR) was completed to detect the interaction between SNPs in PFKP and GPC6 genes to predict the alcohol-induced ONFH risk.

Figure 4 The interacting genes of PFKP and GPC6 were displayed by String software.

Figure 5 The results of the top 10 GO pathways of the interacting genes of PFKP and GPC6. (A) Bubble plot of BP, (B) Bubble plot of MF, (C)Bubble plot of CC.   

Figure 6 The results of the top 10 KEGG pathways of the interacting genes of PFKP and GPC6.