Differential distribution of gene polymorphisms associated with hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia among Native American and Mestizo Mexicans

doi:10.4254/wjh.v14.i7.1408

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World Journal of Hepatology

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World J Hepatol. Jul 27, 2022; 14(7): 1408-1420
Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1408

Table 1 Clinical characteristics and lipid profile of West Mexico populations

Variables	Native American ancestry		Mestizos (low-to-high European ancestry)					Total WMX	P value
Variables	NAH	WXK	TPC	GDL	CUQ	VP	SMA	Total WMX	P value
n (%)	84 (9.5)	106 (12.0)	184 (20.8)	321 (36.4)	131 (14.8)	32 (3.6)	26 (2.9)	884 (100)
Age (yr)	29.5 ± 11	43.5 ± 15	52.5 ± 8.3	36.4 ± 12.6	48 ± 15.4	40.4 ± 21.1	44 ± 15	43.7 ± 14.8	0.022^a
Male n (%)	24 (29)	41 (39)	77 (42)	91 (28)	34 (26)	13 (39)	9 (35)	289 (32.7)	0.001^d
Female n (%)	60 (71)	65 (61)	107 (58)	230 (72)	97 (74)	19 (61)	17 (65)	595 (67.3)	0.001^d
BMI (kg/m²)	26.3 ± 4.3	ND	28.3 ± 4.7	33.8 ± 10.3	28.6 ± 5.8	26.4 ± 5.1	25.5 ± 3.8	29.9 ± 7.7	8 × 10^-27^c
TC (mg/dL)	164.3 ± 39.8	190.4 ± 37.1	228.1 ± 49.2	187.7 ± 42.4	182.1 ± 34.4	210 ± 52.6	179.7 ± 37.2	199.3 ± 48.8	1 × 10^-35^a
TG (mg/dL)	151.5 ± 86.2	150.6 ± 98.1	197.3 ± 123.6	161.6 ± 148.3	150.6 ± 95	171.7 ± 93.1	148.9 ± 86.4	169.7 ± 122.5	0.023^a
LDL-c (mg/dL)	95.6 ± 30.3	120.2 ± 31.7	158.4 ± 46.4	114.5 ± 36.9	107.3 ± 9.1	141.5 ± 38.3	111.3 ± 30.3	128.8 ± 44.7	1 × 10^-30^a
VLDL-c (mg/dL)	29.1 ± 28.6	24.8 ± 10.6	29 ± 16	32.6 ± 30.4	30.3 ± 19.2	36.2 ± 23.3	29.8 ± 17.3	30.4 ± 23.0	0.350
HDL-c (mg/dL)	39.5 ± 6.8	46.2 ± 10.6	41.1 ± 10.8	42.5 ± 14.4	44.0 ± 9.6	43 ± 3.5	39.9 ± 8.1	42.3 ± 11.2	0.010^b

^aTepic (TPC) vs the other groups by post hoc tests, P = 0.002.

^bNahua (NAH) vs Cuquio (CUQ) & Wixárika group by post hoc tests, P = 0.015.

^cGuadalajara (GDL) & NAH vs the other groups by post hoc tests, P = 0.001.

^dTPC vs GDL, NAH & CUQ by post hoc tests, P = 0.035.

Values are presented as mean ± SD. Gender is expressed as number of cases and percentage. The one-way ANOVA for quantitative variables and Chi-square test for qualitative variables were the statistical approach. NAH: Nahua indigenous group; WXK: Wixárika indigenous group; ND: No data; TPC: Tepic; GDL: Guadalajara; CUQ: Cuquio; VP: Villa Purificación; SMA: San Miguel el Alto; WMX: West Mexico; BMI: Body mass index; TC: Total cholesterol; TG: Triglycerides; LDL-c: Low-density lipoprotein cholesterol; VLDL: Very low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol.

Table 2 Prevalence of the type of dyslipidemias in West Mexico populations

Dyslipidemia	Native American ancestry		Mestizos (low-to-high European ancestry)					Total WMX (n = 884)	P value
Dyslipidemia	NAH (n = 84)	WXK (n = 106)	TPC (n = 184)	GDL (n = 321)	CUQ (n = 131)	VP (n = 32)	SMA (n = 26)	Total WMX (n = 884)	P value
HChol	6 (7.1)	41 (38.7)	139 (75.5)	113 (35.2)	43 (32.8)	21 (65.6)	11 (42.3)	374 (42.3)	0.001^a
HTG	35 (41.7)	36 (34.0)	94 (51.1)	116 (36.1)	49 (37.4)	15 (46.9)	12 (46.2)	357 (40.4)	0.001^b
High LDL-c	13 (15.5)	43 (40.6)	137 (74.5)	72 (22.4)	24 (18.3)	21 (65.6)	7 (26.9)	317 (35.8)	0.003^a
HALP	42 (50.0)	28 (26.4)	87 (47.3)	112 (34.9)	45 (34.3)	5 (15.6)	15 (57.7)	334 (37.8)	0.002^c

^aTepic (TPC) vs the other groups.

^bTPC vs Wixárika (WXK) & Cuquio (CUQ) group.

^cVilla Purificación & WXK vs the other groups.

The Chi-square test was the statistical approach. Values are presented as number of cases and percentage. NAH: Nahua indigenous group; WXK: Wixárika indigenous group; TPC: Tepic; GDL: Guadalajara; CUQ: Cuquio; VP: Villa Purificación; SMA: San Miguel el Alto; WMX: West Mexico; HChol: Hypercholesterolemia; HTG: Hypertriglyceridemia; HALP: Hypoalphalipoproteinemia.

Table 3 Frequency of risk allele of polymorphisms associated with lipid disorders in West Mexican populations

Lipid abnormality	SNPs (risk allele)	Native American ancestry		Mestizos (low-to-high European ancestry)					Total WMX (n = 1324)	P value
Lipid abnormality	SNPs (risk allele)	NAH (n = 84)	WXK (n = 106)	TPC (n = 184)	GDL (n = 754)	CUQ (n = 131)	VP (n = 32)	SMA (n = 33)	Total WMX (n = 1324)	P value
Low HDL-c	ABCA1 R230C (RC + CC genotypes)	15 (17.9)	43 (40.6)	24 (13.0)	53 (7.0)	18 (13.7)	4 (12.5)	2 (6.1)	159 (12.0)	0.010^c
High TC^e	APOE (E4 allele)	21 (12.5)	53 (25.0)	ND	145 (9.6)	ND	2 (3.1)	2 (3.0)	223 (8.4)	2 × 10^-12^a
	APOB-516C/T (T allele)	49 (29.2)	58 (27.4)	ND	433 (28.7)	ND	24 (37.5)	18 (27.3)	582 (22.0)	0.129
	LDLR A1413G (G allele)	121 (72.0)	161 (75.9)	ND	1045 (69.3)	ND	42 (65.6)	44 (66.7)	1413 (53.5)	0.047^a
	LDLR C*52T (C allele)	124 (73.8)	145 (68.4)	ND	1068 (70.8)	ND	55 (85.9)	52 (78.8)	1444 (54.7)	0.045^b
High TG^e	APOE (E2 allele)	0 (0)	0 (0)	ND	51 (3.4)	ND	1 (1.6)	7 (10.6)	59 (2.2)	0.028^d
	MTTP-493G/T (T allele)	17 (10.1)	2 (0.9)	ND	253 (16.8)	ND	11 (17.2)	10 (15.2)	293 (11.1)	2 × 10^-6^b
	MTHFR C677T (T allele)	103 (61.3)	111 (52.4)	172 (46.7)	670 (44.4)	117 (44.6)	25 (39.1)	21 (31.8)	930 (35.2)	0.038^b

^aNahua & Wixárika (WXK) vs the other groups.

^bVilla Purificación & San Miguel el Alto (SMA) vs the other groups.

^cWXK vs the other groups.

^dSMA vs the other groups. The Chi-square test was the statistical approach.

^eThe allelic frequencies were obtained considering the diploid number of chromosomes (2n).

Values are expressed as n (%). NAH: Nahua indigenous group; WXK: Wixárika indigenous group; TPC: Tepic; GDL: Guadalajara; VP: Villa Purificación; SMA: San Miguel el Alto; WMX: West Mexico; ND: No data; HDL-c: High-density Lipoprotein cholesterol; TC: Total Cholesterol; TG: Triglycerides.

Table 4 Clinical and biochemical characteristics and frequency of dyslipidemias in normal weight Mestizos individuals

Variable	Reference values	Study group
n		193
Age (yr)		32.8 ± 12.3
Male		55 (28.5%)
Female		138 (71.5%)
BMI (kg/m²)	18.5-24.9	22.3 ± 1.1
Total body fat (%)	< 24%	21.3 ± 6.1
Glucose (mg/dL)	< 100	84.4 ± 7.9
HOMA-IR	< 2.5	1.7 ± 0.5
TC (mg/dL)	< 200	180.1 ± 33.1
TG (mg/dL)	< 150	112.2 ± 61.3
LDL-c (mg/dL)	< 130	109.2 ± 27.6
VLDL-c (mg/dL)	< 25	22.5 ± 12.3
HDL-c (mg/dL)	> 40	49.4 ± 13.7
AST (UI/L)	< 54	26.3 ± 10.5
ALT (UI/L)	< 42	25.1 ± 14.1
GGT (UI/L)	< 35	20.2 ± 5.3
Dyslipidemia		75 (38.9%)
HChol	(TC > 200 mg/dL)	54 (27.9%)
HTG	(TG > 150 mg/dL)	35 (18.1%)
High LDL-c	(LDL-c ≥ 130 mg/dL)	39 (20.2%)
HALP	(HDL-c < 40 mg/dL)	40 (20.7%)

Values are presented as mean ± SD; n: Number of cases and percentage. MTZ: Mestizo; BMI: Body mass index; HOMA-IR: Homeostasis model assessment insulin resistance; TC: Total cholesterol; TG: Triglycerides; LDL-c: Low-density lipoprotein cholesterol; VLDL-c: Very low-density lipoprotein cholesterol; HDL: High-density lipoprotein cholesterol; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl-transferase; HChol: Hypercholesterolemia; HTG: Hypertriglyceridemia; HALP: Hypoalphalipoproteinemia.

Table 5 Association of APOB -516C/T and LDLR A1413G polymorphism with lipid levels in normal weight Mestizos individuals

Variable	*APOB* -516 C/T genotypes			P value	*LDLR* A1413G genotypes			P value
Variable	CC (n = 85)	CT (n = 54)	TT (n = 15)	P value	AA (n = 22)	AG (n = 65)	GG (n = 63)	P value
TC (mg/dL)	177.8 ± 31	178.2 ± 37.4	196.2 ± 27.6	0.033^a	177.2 ± 25.7	175.4 ± 33.1	182.9 ± 34.7	0.366
TG (mg/dL)	110.4 ± 68	119.9 ± 71.3	108.7 ± 25.9	0.574	106.9 ± 47.5	98.7 ± 44.6	124.3 ± 79.8	0.094
LDL-c (mg/dL)	106.3 ± 24	107.3 ± 30.6	129.5 ± 31.6	0.017^a	103.3 ± 23.9	106.2 ± 26.8	111.8 ± 29.5	0.042^b
VLDL-c (mg/dL)	22 ± 13.6	24.3 ± 14.3	21.8 ± 5.1	0.451	21.3 ± 9.5	19.7 ± 9.0	25.1 ± 16.0	0.075
HDL-c (mg/dL)	49.3 ± 13.9	48.5 ± 10.7	50.3 ± 16.9	0.908	51.1 ± 15.3	51.6 ± 11.8	46.8 ± 13.3	0.143
Dyslipidemia, n (%)
HChol	9 (11)	8 (15)	6 (40)	0.012^a	1 (5)	8 (12)	14 (22)	0.034^b
HTG	15 (18)	14 (26)	0 (0)	0.076	3 (14)	7 (11)	15 (24)	0.315
High LDL-c	13 (15)	12 (22)	7 (47)	0.007^a	3 (14)	10 (15)	17 (27)	0.046^b
HALP	19 (22)	10 (18)	3 (20)	0.760	3 (14)	8 (12)	18 (13)	0.178

^aTT vs CC.

^bGG vs AA.

The Kruskall Wallis test and U Mann-Whitney test for quantitative variables and Chi-square test for qualitative variables were the statistical approach. Values are expressed as mean ± SD, number of cases and percentage. MTZ: Mestizos; TC: Total cholesterol; TG: Triglycerides; LDL-c: Low-density lipoprotein cholesterol; VLDL-c: Very low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; HChol: Hypercholesterolemia; HTG: Hypertriglyceridemia; HALP: Hypoalphalipoproteinemia.

Table 6 Association of APOB and LDLR genotypes with hypercholesterolemia in normal weight Mestizos individuals

Genotype	Non-HChol	HChol	P value	Genotype comparison	Odds ratio (95%CI)	P value
APOB -516C/T genotypes
CC	76 (58.0%)	9 (39.1%)	0.120	TT vs CC	5.33 (1.537-18.502)	0.008
CT	46 (35.1%)	8 (34.8%)	0.895	TT vs CC + CT	4.63 (1.463-14.634)	0.009
TT	9 (6.9%)	6 (26.1%)	0.005	TT vs CT	3.83 (1.069-13.746)	0.039
LDLR A1413G genotypes
AA	21 (16.5%)	1 (4.3%)	0.135	GG vs AA	3.90 (1.042-14.583)	0.043
AG	57 (44.9%)	8 (34.8%)	0.340	GG vs AA + AG	2.53 (1.216-5.282)	0.013
GG	49 (38.6%)	14 (60.9%)	0.043	GG vs AG	2.24 (1.028-4.890)	0.042

Values are expressed as number of cases and percentage. MTZ: Mestizos; HChol: Hypercholesterolemia. The Chi-square test and logistic regression test were the statistical approach.

Table 7 Increased serum level of low-density lipoprotein cholesterol associated with APOB and LDLR genotypes in individuals with normal weight from West Mexico

Genotype comparison	R²	β	95%CI	P value
APOB -516C/T
TT vs CC	0.30	40.39	14.415-66.366	0.004
TT vs CC + CT	0.23	39.79	16.226-63.363	0.001
TT vs CT	0.31	39.01	0.996-67.029	0.091
LDLR A1413G
GG vs AA	0.11	23.29	1.640-44.946	0.036
GG vs AA + AG	0.11	20.77	5.763-35.784	0.007
GG vs AG	0.08	19.74	0.915-37.270	0.082

Linear regression test was the statistical approach.

Citation: Torres-Valadez R, Roman S, Ojeda-Granados C, Gonzalez-Aldaco K, Panduro A. Differential distribution of gene polymorphisms associated with hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia among Native American and Mestizo Mexicans. World J Hepatol 2022; 14(7): 1408-1420
URL: https://www.wjgnet.com/1948-5182/full/v14/i7/1408.htm
DOI: https://dx.doi.org/10.4254/wjh.v14.i7.1408