Abstract
This study aimed to examine the possible association between G-395A polymorphism in the promoter region of the KLOTHO gene and cognitive impairment among Chinese nonagenarians and centenarians. This study is a secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study. Community-dwelling Chinese people aged 90 years or older were included. G-395A (rs1207568) genotyping in the promoter region of the KLOTHO gene was performed using the TaqMan allelic discrimination assay. Cognitive function was assessed with the mini-mental status examination (MMSE). A total of 706 participants (68.0 % female; mean age 93.5 ± 3.6 years) were included. The KLOTHO G-395A polymorphism genotype frequencies for the whole sample were 2.0 % AA, 30.3 % GA, and 67.7 % GG. The GG genotype frequencies for the cognitive impairment and control groups were 70.2 and 62.7 %, respectively. Cognitive impairment prevalence was significantly lower in the GA+AA group than in the GG genotype group (61.4 vs. 69.0 %, p = 0.044). GA+AA genotype subjects had a significantly lower risk of cognitive impairment (odds ratio 0.66; 95 % confidence interval 0.44 to 0.98) than GG genotype individuals after adjusting for age, gender, and other relevant risk factors. KLOTHO G-395A polymorphism associates with reduced cognitive impairment in a sample of Chinese nonagenarians and centenarians.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chobanian AV et al (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:1206–1252. doi:10.1161/01.HYP.0000107251.49515.c2
Cui GH et al (2011) Cognitive impairment using education-based cutoff points for CMMSE scores in elderly Chinese people of agricultural and rural Shanghai China. Acta Neurol Scand 124:361–367. doi:10.1111/j.1600-0404.2010.01484.x
Deary IJ, Harris SE, Fox HC, Hayward C, Wright AF, Starr JM, Whalley LJ (2005) KLOTHO genotype and cognitive ability in childhood and old age in the same individuals. Neurosci Lett 378:22–27. doi:10.1016/j.neulet.2004.12.005
Di Bona D, Accardi G, Virruso C, Candore G, Caruso C (2014) Association of Klotho polymorphisms with healthy aging: a systematic review and meta-analysis. Rejuvenation Res 17:212–216. doi:10.1089/rej.2013.1523
Dubal DB et al (2014) Life extension factor klotho enhances cognition. Cell Rep 7:1065–1076. doi:10.1016/j.celrep.2014.03.076
Dubal DB et al (2015) Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. J Neurosci 35:2358–2371. doi:10.1523/JNEUROSCI.5791-12.2015
Holtsberg PA, Poon LW, Noble CA, Martin P (1995) Mini-mental state exam status of community-dwelling cognitively intact centenarians. Int Psychogeriatr 7:417–427
Imamura A, Okumura K, Ogawa Y, Murakami R, Torigoe M, Numaguchi Y, Murohara T (2006) Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese. Clin Chim Acta 371:66–70. doi:10.1016/j.cca.2006.02.021
Katzman R et al (1988) A Chinese version of the mini-mental state examination: impact of illiteracy in a Shanghai dementia survey. J Clin Epidemiol 41:971–978
Kawano K et al (2002) Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 17:1744–1751. doi:10.1359/jbmr.2002.17.10.1744
Kim Y et al (2006) Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females. Neurosci Lett 407:189–194. doi:10.1016/j.neulet.2006.08.039
Kim Y et al (2008) Polymorphism in the promoter region of the klotho gene (G-395A) is associated with early dysfunction in vascular access in hemodialysis patients. Korean J Intern Med 23:201–207. doi:10.3904/kjim.2008.23.4.201
Kuro-o M (2009) Klotho and aging. Biochim Biophys Acta 1790:1049–1058. doi:10.1016/j.bbagen.2009.02.005
Kuro-o M et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51. doi:10.1038/36285
Mellitus ECotDCoD (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–20
Nabeshima Y (2002) Klotho: a fundamental regulator of aging. Ageing Res Rev 1:627–638
Nagai T et al (2003) Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress. FASEB J 17:50–52. doi:10.1096/fj.02-0448fje
Rhee EJ et al (2006) The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease. Metabolism 55:1344–1351. doi:10.1016/j.metabol.2006.05.020
Rosli R, Tan MP, Gray WK, Subramanian P, Chin AV (2015) Cognitive assessment tools in Asia: a systematic review. Int Psychogeriatr 9:1–22. doi:10.1017/S1041610215001635
Semba RD, Moghekar AR, Hu J, Sun K, Turner R, Ferrucci L, O’Brien R (2014) Klotho in the cerebrospinal fluid of adults with and without Alzheimer’s disease. Neurosci Lett 558:37–40. doi:10.1016/j.neulet.2013.10.058
Shimokata H, Ando F, Fukukawa Y, Nishita Y (2006) Klotho gene promoter polymorphism and cognitive impairment. Geriatr Gerontol Int 6:136–141. doi:10.1111/j.1447-0594.2006.00335.x
Tombaugh TN, McIntyre NJ (1992) The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 40:922–935
Tsezou A, Furuichi T, Satra M, Makrythanasis P, Ikegawa S, Malizos KN (2008) Association of KLOTHO gene polymorphisms with knee osteoarthritis in Greek population. J Orthop Res 26:1466–1470. doi:10.1002/jor.20634
Tsolaki M (2014) Clinical workout for the early detection of cognitive decline and dementia. Eur J Clin Nutr 68:1186–1191. doi:10.1038/ejcn.2014.189
Wang Y, Sun Z (2009) Current understanding of klotho. Ageing Res Rev 8:43–51. doi:10.1016/j.arr.2008.10.002
Wang HL et al (2010) A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population. Clin Chim Acta 411:386–390. doi:10.1016/j.cca.2009.12.004
Ward A, Arrighi HM, Michels S, Cedarbaum JM (2012) Mild cognitive impairment: disparity of incidence and prevalence estimates. Alzheimers Dement 8:14–21. doi:10.1016/j.jalz.2011.01.002
Xiao NM, Zhang YM, Zheng Q, Gu J (2004) Klotho is a serum factor related to human aging. Chin Med J 117:742–747
Yamada Y, Ando F, Niino N, Shimokata H (2005) Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women. J Mol Med 83:50–57. doi:10.1007/s00109-004-0578-4
Yokoyama JS et al (2015) Variation in longevity gene KLOTHO is associated with greater cortical volumes. Ann Clin Transl Neurol 2:215–230. doi:10.1002/acn3.161
Yue JR, Dong BR, Huang CQ, Lu ZC, Wu HM, Zhang YL (2010) Pro12Ala polymorphism in PPAR-gamma2 and dementia in Chinese nonagenarians/centenarians. Age (Dordr) 32:397–404. doi:10.1007/s11357-010-9132-1
Zhang F, Zhai G, Kato BS, Hart DJ, Hunter D, Spector TD, Ahmadi KR (2007) Association between KLOTHO gene and hand osteoarthritis in a female Caucasian population. Osteoarthritis Cartilage 15:624–629. doi:10.1016/j.joca.2006.12.002
Zhou Y, Huang CQ, Lu ZC, Dong BR (2012) Association of serum uric acid with Pro12Ala polymorphism in PPAR-gamma2 among Chinese nonagenarians/centenarians. Aging Clin Exp Res 24:139–144. doi:10.3275/8018
Zhu AH, Tian JZ, Zhong J, Yang CZ, Shi J, Yin JX (2006) A clinical study on a randomized, double-blind control of Chinese medicine granules in treatment of vascular dementia. Zhongguo Zhong Yao Za Zhi 31:1722–1725
Acknowledgments
The authors thank the staff of the Department of Geriatrics, Dujiangyan Hospital, and all participants and legal proxies for their great contributions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Written informed consent was obtained from all subjects or their legal proxies. The Research Ethics Committee of Sichuan University approved the study protocol.
Conflict of interests
The authors declare that they have no competing interests.
Funding sources
This work was supported by the Project of Science and technology Bureau of Sichuan Province (2006Z09-006-4) and the Health Care Committee of Sichuan Province Health Department (2012-GANJIANBAN-7). The sponsor had no role in the design, methods, data collection, analysis, and preparation of this paper.
About this article
Cite this article
Hao, Q., Ding, X., Gao, L. et al. G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old. AGE 38, 7 (2016). https://doi.org/10.1007/s11357-015-9869-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11357-015-9869-7