Lack of functional KL-VS polymorphism of the <i>KLOTHO</i> gene in the Korean population

Kim, Hee-Kwon; Jeong, Byung-Hoon

doi:10.1590/1678-4685-GMB-2015-0160

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Human and Medical Genetics • Genet. Mol. Biol. 39 (3) • Jul-Sep 2016 • https://doi.org/10.1590/1678-4685-GMB-2015-0160 copy

Lack of functional KL-VS polymorphism of the KLOTHO gene in the Korean population

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The functional variant of the Klotho "KL-VS" stretch, which includes six polymorphisms in linkage disequilibrium, is reportedly associated with healthy aging and longevity in European and American populations. Among Asian populations, this variant has been observed in the Indian population but not in the Iranian population. An association between KL-VS polymorphism and aging has not been reported in Koreans. To investigate whether the KL-VS polymorphism could be associated with healthy aging and longevity in a Korean population, we analyzed genotype and allele frequencies of the KL-VS variant in a large Korean population sample. The KL-VS variant was not found in 874 Korean individuals. Thus, it is not possible to test its association to aging in the East Asian populations.

Keywords
Aging; KLOTHO gene; KL-VS polymorphism; population genetics

Population	Age, yr	Total	Genotype, n (%)			P-value	Allele, %		P-value	Reference
Population	Age, yr	Total	WT/WT	WT/ VS	VS/VS	P-value	WT	VS	P-value	Reference
UK Caucasian	29-35	1619	1158 (71.5)	409 (25.3)	52 (3.2)	-	84.2	15.8	-	*Freathy et al.,* 2006**Freathy RM, Weedon MN, Melzer D, Shields B, Hitman GA, Walker M, McCarthy MI, Hattersley AT and Frayling TM (2006) The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians. BMC Med Genet 7:e51.
Bohemian Czech	New Born	390	307 (78.7)	73 (18.7)	10 (2.6)	0.016	88.1	11.9	0.006	*Arking et al.,* 2003**Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC and Dietz HC (2003) KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet 72:1154-1161.
	Elderly ≥ 75	415	308 (74.2)	103 (24.8)	4 (0.1)	0.040	86.6	13.4	0.078
Baltimore Caucasian	New Born	420	309 (73.6)	100 (23.8)	11 (2.6)	0.652	85.5	14.5	0.347
	Elderly ≥ 65	723	530 (73.3)	185 (25.6)	8 (1.1)	0.012	86.1	13.9	0.088
Baltimore African American	New Born	226	156 (69.0)	58 (25.7)	12 (5.3)	0.259	81.9	18.1	0.213
Baltimore African American	Elderly ≥ 65	242	169 (69.8)	68 (28.1)	5 (2.1)	0.439	83.9	16.1	0.878
American	Mean 54.3	143	95 (66.4)	44 (30.8)	4 (2.8)	0.350	81.8	18.2	0.302	*Low et al., 2005*Low AF, O'Donnell CJ, Kathiresan S, Everett B, Chae CU, Shaw SY, Ellinor PT and MacRae CA (2005) Aging syndrome genes and premature coronary artery disease. BMC Med Genet 6:e38.
US Caucasian	<35	332	241 (72.6)	85 (25.6)	6 (1.8)	0.390	85.4	14.6	0.425	*Novelli et al., 2008*Novelli V, Viviani Anselmi C, Roncarati R, Guffanti G, Malovini A, Piluso G and Puca AA (2008) Lack of replication of genetic associations with human longevity. Biogerontology 9:85-92.
	93-105	708	517 (73.0)	170 (24.0)	21 (3.0)	0.757	85.0	15.0	0.451
Spanish	18-86 (mean 48.0)	438	330 (75.3)	104 (23.8)	4 (0.9)	0.021	87.2	12.8	0.025	*Riancho et al.,* 2007**Riancho JA, Valero C, Hernández JL, Ortiz F, Zarrabeitia A, Alonso MA, Peña N, Pascual MA, González-Macías J and Zarrabeitia MT (2007) Association of the F352V variant of the Klotho gene with bone mineral density. Biogerontology 8:121-127.
Greek	Men (mean 61.5), Women (mean 65.8)	383	309 (80.7)	71 (18.4)	3 (0.8)	<0.001	90.0	10.0	<0.001	*Tsezou et al.,* 2008**Tsezou A, Furuichi T, Satra M, Makrythanasis P, Ikegawa S and Malizos KN (2008) Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population. J Orthop Res 26:1466-1670.
Italian	Men <66, Women <73	463	348 (75.2)	103 (22.2)	12 (2.6)	0.300	86.3	13.7	0.113	*Invidia et al.,* 2010**Invidia L, Salvioli S, Altilia S, Pierini M, Panourgia MP, Monti D, De Rango F, Passarino G and Franceschi C (2010) The frequency of Klotho KL-VS polymorphism in a large Italian population, from young subjects to centenarians, suggests the presence of specific time windows for its effect. Biogerontology 11:67-73.
	Men 66-88, Women 73-91	300	203 (67.7)	94 (31.3)	3 (1.0)	0.140	83.3	16.7	0.613
	Men >88, Women >91	326	236 (72.4)	80 (24.5)	10 (3.1)	0.950	84.7	15.3	0.746
French	25-88 (mean 57.5)	629	436 (69.3)	172 (27.4)	21 (3.3)	0.579	83.0	17.0	0.340	*Nzietchueng et al.,* 2011**Nzietchueng RE, Shamieh S, Benachour H, Labat C, Herbeth B, Ndiaye NC, Masson C, Visvikis-Siest S and Benetos A (2011) Klotho KL-VS genotype is involved in blood pressure regulation. Clin Chim Acta 412:1773-1777.
Iranian	Mean 55	53	53 (100)	0 (0)	0 (0)	<0.001	100	0	<0.001	*Tavakkoly-Bazzaz et al.,* 2011**Tavakkoly-Bazzaz J, Tabatabaei-Malazy O, Tajmir-Riahi M, Javidi D, Izadi M, Shahrabi-Farahani M, Amiri P and Amoli MM (2011) Absence of kl-vs variant of klotho gene in Iranian cardiac patients (comparison to the world populations). Dis Markers 31:211-214.
Indian	≤ 40	375	270 (72.0)	99 (26.4)	6 (1.6)	0.237	85.2	14.8	0.479	*Majumdar et al.,* 2010**Majumdar V, Nagaraja D and Christopher R (2010) Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke. Biochem Biophys Res Commun 403:412-416.
	>40	199	140 (70.4)	53 (26.6)	6 (3.0)	0.911	83.7	16.3	0.801
Korean	≤ 40 (mean 27.0)	101	101 (100)	0 (0)	0 (0)	<0.001	100	0	<0.001	This study
	40-79 (mean 62.9)	671	671 (100)	0 (0)	0 (0)	<0.001	100	0	<0.001
	≥ 80 (mean 85.8)	102	102 (100)	0 (0)	0 (0)	<0.001	100	0	<0.001

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[1] Send correspondence to Byung-Hoon Jeong, Korea Zoonosis Research Institute, Chonbuk National University, 820-120 Hana-ro, Iksan, Jeonbuk 570-390, Republic of Korea. E-mail: bhjeong@jbnu.ac.kr