RAB40C Gene Polymorphisms Were Associated with Alcohol-Induced Osteonecrosis of the Femoral Head

Figures & data

Table 1 Comparison of Clinical Data in Case and Control Groups

Characteristic	Case	Control	p-value
Number	201	201
Age(years, Mean ± SD)	42.68 ± 12.88	42.87 ± 13.27	0.888^a
BMI (kg/m^2, Mean ± SD)	21.15 ± 2.70	21.33 ± 2.87	0.383^a
Drinking			0.688^b
Yes	199(99%)	199(99%)
Deletion	2(1%)	2(1%)
Smoking			0.527^b
No	20(10%)	25(12.4%)
Yes	179(90%)	176(87.6%)
Hip lesions
Unilateral	44 (22%)
Bilateral	157 (78%)
Clinical stages
I+II	54 (27%)
III+IV	147 (73%)

Notes: ^aIndependent samples t test; ^bPearson Chi-squared test. p < 0.05 indicates statistical significance.

Abbreviation: SD, standard deviation.

Table 2 Basic Information of the Three SNPs in This Study

SNP ID	Gene	Chr	Position	Role	Alleles A/B	MAF		HWE p-value	OR (95% CI)	p^a
						Case	Control
Rs4984677	RAB40C	16p13.3	621,682	Intronic	A/G	0.392	0.356	1.000	1.17 (0.88–1.56)	0.290
Rs62030917	RAB40C	16p13.3	622,040	Intronic	G/A	0.295	0.221	0.218	1.47 (1.07–2.02)	0.017*
Rs2269556	RAB40C	16p13.3	625,215	UTR3	G/A	0.413	0.381	0.767	1.14 (0.86–1.52)	0.356

Notes: ^aPearson Chi-squared test; *p< 0.05 indicates statistical significance.

Abbreviations: SNP, single nucleotide polymorphism; Chr, chromosome; Alleles A/B, Minor/Major alleles; HWE, Hardy Weinberg equilibrium; MAF, minor allele frequency; OR, odds ratio; 95% CI, 95% confidence interval.

Table 3 Association Analysis Between SNPs and Alcohol-Induced ONFH Risk

SNP ID	Model	Genotype	Case	Control	Without Adjusted		Adjusted
					OR (95% CI)	p	OR (95% CI)	p
rs4984677	Co-dominant	G/G	75 (37.69%)	83 (41.29%)	1		1
		A/G	92 (46.23%)	93 (46.27%)	1.10 (0.72–1.67)	0.676	1.10 (0.72–1.67)	0.677
		A/A	32 (16.08%)	25 (12.44%)	1.42 (0.77–2.61)	0.263	1.42 (0.77–2.61)	0.263
	Dominant	G/G	75 (37.69%)	83 (41.29%)	1		1
		A/G-A/A	124 (62.31%)	118 (58.71%)	1.16 (0.78–1.74)	0.461	1.16 (0.78–1.74)	0.461
	Recessive	G/G-A/G	167 (83.92%)	176 (87.56%)	1		1
		A/A	32 (16.08%)	25 (12.44%)	1.35 (0.77–2.37)	0.299	1.35 (0.77–2.37)	0.299
	Log-additive	---	---	---	1.17 (0.88–1.55)	0.293	1.17 (0.88–1.55)	0.293
Rs62030917	Co-dominant	A/A	104 (52%)	125 (62.19%)	1		1
		G/A	74 (37%)	63 (31.34%)	1.41 (0.92–2.16)	0.112	1.41 (0.92–2.16)	0.112
		G/G	22 (11%)	13 (6.47%)	2.03 (0.98–4.24)	0.058	2.04 (0.98–4.24)	0.058
	Dominant	A/A	104(52%)	125(62.19%)	1		1
		G/A-G/G	96(48%)	76(37.81%)	1.52 (1.02–2.26)	0.039*	1.52 (1.02–2.26)	0.039*
	Recessive	A/A-G/A	178(89%)	188(93.53%)	1		1
		G/G	22(11%)	13(6.47%)	1.79 (0.87–3.66)	0.112	1.79 (0.87–3.66)	0.112
	Log-additive	---	---	---	1.42 (1.05–1.93)	0.024*	1.42 (1.05–1.93)	0.025*
Rs2269556	Co-dominant	A/A	72(36%)	78(38.8%)	1		1
		G/A	91(45.5%)	93(46.27%)	1.06 (0.69–1.63)	0.791	1.06 (0.69–1.63)	0.792
		G/G	37(18.4%)	30(14.93%)	1.34 (0.75–2.38)	0.326	1.34 (0.75–2.38)	0.327
	Dominant	A/A	72(36%)	78(38.81%)	1		1
		G/A-G/G	128(64%)	123(61.19%)	1.13 (0.75–1.69)	0.562	1.13 (0.75–1.69)	0.563
	Recessive	A/A-G/A	163(81.5%)	171(85.07%)	1		1
		G/G	37(18.5%)	30(14.93%)	1.29 (0.76–2.19)	0.338	1.29 (0.76–2.19)	0.339
	Log-additive	---	---	---	1.14 (0.86–1.50)	0.366	1.14 (0.86–1.50)	0.367

Notes: *p < 0.05 indicates statistical significance.

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

Table 4 Correlation Analysis of Rs62030917, Rs2269556 and Alcohol-Induced ONFH After Stratificated by Age and Hip Lesions in Different Genetic Models

SNP	Model	Genotype	≤42		>42		Unilateral		Bilateral
			OR(95% CI)	p	OR(95% CI)	p	OR(95% CI)	p	OR(95% CI)	p
Rs62030917	Co-dominant	A/A	1		1		1		1
		G/A	1.24 (0.67–2.28)	0.494	1.61 (0.88–2.91)	0.120	2.20 (1.08–4.45)	0.036*	1.25 (0.79–1.97)	0.343
		G/G	3.00 (1.08–8.30)	0.035*	1.21 (0.40–3.65)	0.742	3.20 (1.08–9.48)	0.029*	1.79 (0.82–3.92)	0.144
	Dominant	A/A	1		1		1		1
		G/A-G/G	1.51 (0.86–2.66)	0.152	1.53 (0.87–2.68)	0.139	2.37 (1.22–4.61)	0.011*	1.34 (0.88–2.05)	0.178
	Recessive	A/A-G/A	1		1		1		1
		G/G	2.77 (1.03–7.47)	0.044*	1.01 (0.34–3.00)	0.984	2.28 (0.82–6.38)	0.116	1.65 (0.77–3.55)	0.197
	Log-additive	---	1.53 (1.00–2.33)	0.048	1.31 (0.84–2.04)	0.239	1.90 (1.18–3.08)	0.009*	1.30 (0.94–1.80)	0.114
	Alleles	G/A	1.62 (1.04–2.54)	0.033*	1.33 (0.84–2.09)	0.224	2.01 (1.23–3.29)	0.005*	1.34 (0.95–1.88)	0.095
Rs2269556	Co-dominant	A/A	1		1		1		1
		G/A	0.94 (0.50–1.73)	0.831	1.20 (0.65–2.20)	0.565	1.59 (0.72–3.51)	0.247	0.96 (0.61–1.52)	0.870
		G/G	1.19 (0.53–2.66)	0.671	1.51 (0.66–3.48)	0.333	2.83 (1.13–7.10)	0.027*	1.07 (0.57–2.00)	0.841
	Dominant	A/A	1		1		1		1
		G/A-G/G	1.00 (0.56–1.78)	0.995	1.27 (0.71–2.25)	0.419	1.90 (0.90–3.97)	0.090	0.99 (0.64–1.52)	0.955
	Recessive	A/A-G/A	1		1		1.00		1
		G/G	1.23 (0.59–2.57)	0.574	1.37 (0.64–2.92)	0.422	2.13 (0.99–4.60)	0.053	1.09 (0.61–1.94)	0.774
	Log-additive	---	1.06 (0.72–1.57)	0.762	1.22 (0.82–1.82)	0.325	1.68 (1.06 −2.67)	0.028*	1.02 (0.75–1.37)	0.913
	Alleles	G/A	1.07 (0.71–1.59)	0.758	1.22 (0.82–1.82)	0.320	1.70 (1.07–2.71)	0.023*	1.02 (0.75–1.38)	0.913

Notes: *p < 0.05 indicates statistical significance.

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

Table 5 Comparative Analysis of Plasma Lipoprotein and Lipid Levels in Carrier with Different Genotypes of Rs4984677, Rs62030917 and Rs2269556

SNP		TC (mmol/L)	TG (mmol/L)	HDL-C (mmol/L)	LDL-C (mmol/L)	PLT (10^9/L)
Rs4984677	AA(n=32)	4.70± 1.05	1.69± 0.85	1.03± 0.25	2.91± 1.06	228.53±71.16
	AG(n=92)	4.74± 0.91	1.88± 1.20	1.06± 0.24	2.77± 0.84	229.51±53.58
	GG(n=75)	4.50± 0.86	1.99± 1.53	1.02± 0.22	2.58± 0.71	230.13±60.63
	p	0.244	0.551	0.366	0.120	0.964
Rs62030917	AA(n=104)	4.59± 0.89	2.02± 1.42	1.03± 0.23	2.65± 0.84	230.94±62.13
	GA(n=74)	4.73± 0.92	1.73± 1.17	1.08± 0.25	2.81± 0.78	227.58±53.90
	GG(n=22)	4.63± 1.07	1.85± 0.88	0.99± 0.24	2.82± 1.13	232.41±75.66
	p	0.611	0.331	0.225	0.387	0.916
Rs2269556	AA(n=72)	4.52± 0.88	2.04± 1.55	1.02± 0.22	2.55± 0.71	228.54±66.49
	GA(n=91)	4.72± 0.89	1.81± 1.20	1.07± 0.24	2.78± 0.83	231.65±52.81
	GG(n=37)	4.76± 1.06	1.79± 0.85	1.03± 0.26	2.95± 1.08	227.43±67.48
	p	0.296	0.472	0.396	0.047*	0.918

Notes: *p < 0.05 indicates statistical significance.

Abbreviations: TC, Total cholesterol; TG, Triglycerides; LDL-C, Low-density lipoprotein-cholesterol; HDL-C, High-density lipoprotein-cholesterol; ApoA1, Apolipoprotein A1; ApoB, Apolipoprotein B; PLT, platelet count.

Figure 1 In patients with unilateral lesions, LD plots containing three SNPs from RAB40C.

Figure 2 In patients older than 42 years old, LD plots containing three SNPs from RAB40C.