Type 2 diabetes associated variants of <i>KCNQ1</i> strongly confer the risk of cardiovascular disease among the Saudi Arabian population

Al-Shammari, Maha S.; Al-Ali, Rhaya; Al-Balawi, Nader; Al-Enazi, Mansour S.; Al-Muraikhi, Ali A.; Busaleh, Fadi N.; Al-Sahwan, Ali S.; Al-Elq, Abdulmohsen; Al-Nafaie, Awatif N.; Borgio, Jesu Francis; AbdulAzeez, Sayed; Al-Ali, Amein; Acharya, Sadananda

doi:10.1590/1678-4685-GMB-2017-0005

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Human and Medical Genetics • Genet. Mol. Biol. 40 (3) • Jul-Sep 2017 • https://doi.org/10.1590/1678-4685-GMB-2017-0005 copy

Type 2 diabetes associated variants of KCNQ1 strongly confer the risk of cardiovascular disease among the Saudi Arabian population

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Genome-wide association studies have identified several loci associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D). Polymorphisms within the KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) gene are consistently associated with T2D in a number of populations. The current study was undertaken to evaluate the association of 3 polymorphisms of KCNQ1 (rs2237892, rs151290 and rs2237895) with T2D and/or CVD. Patients diagnosed with either T2D (320 patients), CVD (250 patients) or both (60 patients) and 516 healthy controls were genotyped by TaqMan assay run on a real time PCR thermocycler. A statistically significant association was found for SNPs rs151290 (OR = 1.76; 95%CI = 1.02-3.05; p = 0.0435) and rs2237895 (OR = 2.49; 95%CI = 1.72-3.61; p < 0.0001) with CVD. SNP rs151290 (OR = 7.43; 95%CI = 1.00-55.22; p = 0.0499) showed a strong association in patients with both T2D and CVD. None of the SNPs showed any significant association with T2D. Haploview analysis showed that the ACC (rs151290, rs2237892 and rs2237895) haplotype is the most significant risk allele combination for CVD, while CCA is the most significant risk haplotype for co-morbidity with T2D. KCNQ1 polymorphism at SNPs rs151290 and rs2237895 is strongly associated with CVD in this population, but presented no association with T2D.

Keywords:
T2D; CVD; KCNQ1; genetic association; Saudi population

Parameter	Control subjects (n = 516)	T2D patients (n = 320)	CVD patients (n = 250)	T2D + CVD patients (n = 60)
Male (%)	289 (56.01)	174 (54.38)	163 (65.20)	48
Female (%)	227 (43.99) p < 0.0060	146 (45.63) p = 0.1175	87 (34.80) p < 0.0001	12 p < 0.0001
Mean age (years)	48.75 ± 6.85	51.50 ± 8.75 p < 0.8875	52.3 ± 13.8 p < 0.8870	54 ± 9.45 p < 0.7783
Age range (years)	25-65	28-82	32-85	42-78
BMI (kg/m²)	25 ± 3.8	27.2 ± 4.6 p < 0.0001	32.59 ± 5.3 p < 0.0001	33.47 ± 6.5 p < 0.0001
Glucose (mmol/L)	4.92 ± 3.8	8.15 ± 4.2 p < 0.0001	5.22 ± 5.6 p < 0.3837	8.27 ± 3.6 p < 0.0001

SNP variants of KCNQ1	Allele / Genotype	Control subjects (n = 516)	T2D			CVD			T2D + CVD
SNP variants of KCNQ1	Allele / Genotype	Control subjects (n = 516)	Patients (n = 330)	OR (95% CI)	p-value^* * p < 0.05 was considered significant	Patients (n = 250)	OR (95% CI)	p-value^* * p < 0.05 was considered significant	Patients (n = 60)	OR (95% CI)	p-value^* * p < 0.05 was considered significant
rs151290 (A > C)	A allele	275 (26.65)	185 (28.03)	-	-	184 (37.25)	-	-	17 (14.17)	-	-
	C allele	757 (73.35)	475 (71.97)	0.9327 (0.7494-1.1609)	0.5328	310 (62.75)	0.6120 (0.4870-0.7693)	< 0.0001	103 (85.83)	2.2010 (1.2938-3.7443)	0.0036
	AA	49 (9.50)	32 (9.70)	-	-	22 (8.91)	-	-	1 (1.67)	-	-
	AC	177 (34.30)	121 (36.67)	1.0468 (0.6337-1.7291)	0.8583	140 (56.68)	1.7617 (1.0167-3.0525)	0.0435	15 (25.0)	4.1525 (0.5352-32.2197)	0.1732
	CC	290 (56.20)	177 (53.63)	0.9346 (0.5765-1.5151)	0.7838	85 (34.41)	0.6528 (0.3736-1.1407)	0.1342	44 (73.33)	7.4345 (1.0010-55.2165)	0.0499
rs2237892 (C > T)	C allele	1007 (97.58)	647 (98.03)	-	-	484 (97.58)	-	-	120 (100)	-	-
	T allele	25 (2.42)	13 (1.97)	0.8093 (0.4111-1.5934)	0.5405	12 (2.42)	0.9987 (0.4975-2.0047)	0.9970	0 (0)	0.1639 (0.0099-2.7102)	0.2064
	CC	496 (97.12)	319 (96.67)	-	-	236 (95.16)	-	-	60 (100)	-	-
	CT	15 (2.91)	9 (2.73)	0.9329 (0.4034-2.1573)	0.8710	12 (4.84)	1.6814 (0.7748-3.6487)	0.1887	0 (0)	0.2647 (0.0156-4.4807)	0.3571
	TT	5 (0.97)	2 (0.61)	0.6219 (0.1199-3.2251)	0.5717	0 (0)	0.1909 (0.0105-3.4660)	0.2628	0 (0)	0.7461 (0.0407-13.6595)	0.8434
rs2237895 (A > C)	A allele	627 (60.76)	394 (59.70)	-	-	237 (47.59)	-	-	85 (70.83)	-	-
	C allele	405 (39.24)	266 (40.30)	1.0452 (0.8562-1.2760)	0.6641	261 (52.41)	1.7049 (1.3740-2.1154)	< 0.0001	35 (29.17)	0.6375 (0.4218-0.9634)	0.0326
	AA	202 (39.15)	122 (36.97)	-	-	97 (38.96)	-	-	31 (51.67)	-	-
	AC	223 (43.22)	150 (45.45)	1.1137 (0.8205-1.5117)	0.4896	43 (17.27)	0.4016 (0.2674-0.6029)	< 0.0001	23 (38.33)	0.6721 (0.3793-1.1908)	0.1733
	CC	91 (17.63)	58 (17.58)	1.0553 (0.7083-1.5723)	0.7913	109 (43.77)	2.4944 (1.7249-3.6072)	< 0.0001	6 (10.0)	0.4296 (0.1732-1.0658)	0.0684

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E-mail: editor@gmb.org.br

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[1] Send correspondence to Sadananda Acharya, Institute for Research and Medical Consultations (IRMC), University of Dammam, P. O. Box 1982, Dammam, Kingdom of Saudi Arabia - 34541. E-mail: sabaikady@uod.edu.sa.