Lack of association between genetic polymorphism of <i>FTO, AKT1</i> and <i>AKTIP</i> in childhood overweight and obesity

Pereira, Patrícia de Araújo; Alvim-Soares Jr., António Marcos; Sandrim, Valéria Cristina; Lanna, Carla Márcia Moreira; Souza-Costa, Débora Cristine; Belo, Vanessa de Almeida; Paula, Jonas Jardim de; Tanus-Santos, José Eduardo; Romano-Silva, Marco Aurélio; Miranda, Débora Marques de

doi:10.1016/j.jped.2015.12.007

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Original articles • J. Pediatr. (Rio J.) 92 (5) • Sep/Oct 2016 • https://doi.org/10.1016/j.jped.2015.12.007 copy

Lack of association between genetic polymorphism of FTO, AKT1 and AKTIP in childhood overweight and obesity^☆ ☆ Please cite this article as: Pereira PA, Alvim-Soares AM, Sandrim VC, Lanna CM, Souza-Costa DC, Belo VA, et al. Lack of association between genetic polymorphism of FTO, AKT1 and AKTIP in childhood overweight and obesity. J Pediatr (Rio J). 2016;92:521-7.

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Abstract

Objective:

Obesity is a chronic disease caused by both environmental and genetic factors. Epidemiological studies have documented that increased energy intake and sedentary lifestyle, as well as a genetic contribution, are forces behind the obesity epidemic. Knowledge about the interaction between genetic and environmental components can facilitate the choice of the most effective and specific measures for the prevention of obesity. The aim of this study was to assess the association between the FTO, AKT1, and AKTIP genes and childhood obesity and insulin resistance.

Methods:

This was a case-control study in which SNPs in the FTO (rs99396096), AKT1, and AKTIP genes were genotyped in groups of controls and obese/overweight children. The study included 195 obese/overweight children and 153 control subjects.

Results:

As expected, the obese/overweight group subjects had higher body mass index, higher fasting glucose, HOMA-IR index, total cholesterol, low-density lipoprotein, and triglycerides. However, no significant differences were observed in genes polymorphisms genotype or allele frequencies.

Conclusion:

The present results suggest that AKT1, FTO, and AKTIP polymorphisms were not associated with obesity/overweight in Brazilians children. Future studies on the genetics of obesity in Brazilian children and their environment interactions are needed.

KEYWORDS
Single-nucleotide polymorphisms; Childhood obesity; Fat mass and obesity associated; Gene; AKT1; AKTIP

	Control n = 153 (%)	Obese/overweight n = 195 (%)
Female	91 (59.47)	104 (53.33)
Age	11.9 (±3.2)	11.0 (±3.9)
BMI	17.9 (±2.3)	26.7 (±4.5)
SBP	105.3 (±12.4)	118.7 (±15.1)
DBP	65.2 (±9.7)	73.8 (±9.7)
Hypertension	5 (3.2)	61 (31.2)
Glucose (mg/dL)	80.8 (±10.9)	86.0 (±8.8)
HOMA-IR	2.17 (±2.21)	5.68 (±3.28)
Total cholesterol	142 (±43)	145 (±35)
LDL	60.5 (±34)	84.8 (±35)
HDL	44 (±9)	39 (±10)
Triglycerides (mg/dL)	74.3 (±27)	88.2 (±41)

	Obesity/overweight	Control	OR	95% Lo	χ ²	df	p-value (1000 permut.)
	n = 195 (%)	n = 153 (%)		95% Hi
AKT1
rs2494738
G/G	150 (76.92)	126 (82.25)	1 (ref)		1.13	2	0.56
A/G	30 (15.38)	18 (11.76)	1.40	0.73-2.63
A/A	01 (0.5)	1 (0.65)	0.84	0.05-13.57
G ^a a Ancestral allele.	330 (84.62)	270 (88.24)	1 (ref)		0.83	1	0.36
A	32 (8.2)	20 (6.54)	1.30	0.73-2.34
rs3730358
G/G	116 (59.49)	90 (58.82)	1 (ref)		2.31	2	0.31
A/G	54 (27.69)	48 (31.37)	0.87	0.54-1.40
A/A	11 (5.64)	4 (2.61)	2.13	0.65-6.23
G ^a a Ancestral allele.	286 (73.33)	228 (74.51)	1 (ref)		0.15	1	0.68
A	76 (19.49)	56 (18.3)	1.08	0.73-1.59
rs10149779
G/G	94 (48.21)	55 (35.95)	1 (ref)		6.29	2	0.04 (0.09)
G/A	73 (37.44)	76 (49.68)	0.56	0.35-0.89
A/A	18 (9.23)	17 (11.11)	0.61	0.29-1.30
G ^a a Ancestral allele.	261 (37.83)	186 (60.78)	1 (ref)		4.40	1	0.03 (0.20)
A	109 (27.95)	110 (35.95)	0.70	0.51-0.97

AKTIP
rs9302648
T/T	76 (38.97)	46 (30.07)	1 (ref)		7.15	2	0.02 (0.09)
G/T	76 (38.97)	82 (53.59)	0.56	0.34-0.90
G/G	36 (18.46)	21 (13.73)	1.03	0.54-1.98
T ^a a Ancestral allele.	228 (58.46)	174 (56.86)	1 (ref)		0.34	1	0.55
G	148 (37.95)	124 (40.52)	0.91	0.66-1.24
rs7189819
C/C	67 (34.36)	61 (39.87)	1 (ref)		0.95	2	0.61
C/T	84 (43.08)	65 (42.48)	1.17	0.73-1.89
T/T	34 (17.44)	23 (15.03)	1.34	0.71-2.53
C ^a a Ancestral allele.	218 (55.9)	187 (61.11)	1 (ref)		1.01	1	0.31
T	152 (38.97)	111 (36.27)	1.17	0.85-1.60

FTO
rs9939609		rs9939609
A/A	44 (22.56)	34 (22.22)	1 (ref)		4.42	2	0.10
T/A	45 (23.08)	71 (46.41)	1.14	0.66-1.96
T/T	39 (20.0)	46 (30.07)	0.65	0.35-1.21
A ^a a Ancestral allele.	193 (49.49)	139 (45.42)	1 (ref)		1.88	1	0.16
T	183 (46.92)	163 (53.27)	0.80	0.59-1.09

Linear regression models for HOMA
Predictor	F	p	adj R ²	Std. beta	t
AKT1 rs2191738 HEX/FAM A/G	0.00	0.983	0.00	0.01	0.22
AKT1 rs3730358 HEX/FAM A/G	0.12	0.725	0.00	0.02	0.35
AKT1 rs10119779 HEX/FAM A/G	0.02	0.880	0.00	0.01	0.15
FTO rs9939309 HEX/FAM A/T	0.00	0.971	0.00	0.00	0.03
AKTIP rs9302318 HEX/FAM G/T	0.65	0.421	0.00	0.05	0.81
AKTIP rs7189819 HEX/FAM C/T	0.33	0.567	0.00	0.04	0.57

Linear regression models for BMI
Predictor	F	p	adj R ²	Std. beta	t
AKT1 rs2191738 HEX/FAM A/G	0.01	0.919	0.00	0.00	0.10
AKT1 rs3730358 HEX/FAM A/G	0.06	0.802	0.00	-0.01	-0.25
AKT1 rs10119779 HEX/FAM A/G	2.23	0.137	0.00	-0.08	-1.49
FTO rs9939309 HEX/FAM A/T	3.08	0.080	0.01	-0.09	1.75
AKTIP rs9302318 HEX/FAM G/T	0.05	0.816	0.00	0.01	0.23
AKTIP rs7189819 HEX/FAM C/T	1.38	0.240	0.00	-0.06	-1.18

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[1] * Corresponding author. E-mail:antonioalvimjr@gmail.com (A.M. Alvim-Soares Jr.).