Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index.

BACKGROUND The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI). METHODS We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES). RESULTS Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5) were significantly associated (P < 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP (P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure (P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI. CONCLUSIONS Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5, further highlighting the importance of obesity prevention in reducing hypertension risk.

[1]  B. Oh,et al.  ANTXR2 is a potential causative gene in the genome-wide association study of the blood pressure locus 4q21 , 2014, Hypertension Research.

[2]  F. McAlister,et al.  Hypertension prevalence, awareness, treatment and control in national surveys from England, the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a cross-sectional study , 2013, BMJ Open.

[3]  Tao Chen,et al.  Prevalence of Hypertension in China: A Cross-Sectional Study , 2013, PloS one.

[4]  S. Cole,et al.  Sodium Intake from Various Time Frames and Incident Hypertension Among Chinese Adults , 2013, Epidemiology.

[5]  Yanling Hu,et al.  Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects , 2012, PLoS genetics.

[6]  C. Stehouwer,et al.  Microvascular Dysfunction: A Potential Mechanism in the Pathogenesis of Obesity‐associated Insulin Resistance and Hypertension , 2012, Microcirculation.

[7]  Tom R. Gaunt,et al.  Genetic Variants in Novel Pathways Influence Blood Pressure and Cardiovascular Disease Risk , 2011, Nature.

[8]  Z. Mo,et al.  Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey. , 2011, Metabolism: clinical and experimental.

[9]  Tien Yin Wong,et al.  Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians , 2011, Nature Genetics.

[10]  Andrew D. Johnson,et al.  Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals , 2011, Hypertension.

[11]  R. Loos,et al.  Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans , 2011, Journal of hypertension.

[12]  B. Popkin,et al.  Cohort Profile: The China Health and Nutrition Survey--monitoring and understanding socio-economic and health change in China, 1989-2011. , 2010, International journal of epidemiology.

[13]  P. Munroe,et al.  Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension: The Japanese Millennium Genome Project , 2010, Hypertension.

[14]  W. Niu,et al.  Confirmation of top polymorphisms in hypertension genome wide association study among Han Chinese. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[15]  P. O’Reilly,et al.  Faculty Opinions recommendation of Genome-wide association study identifies eight loci associated with blood pressure. , 2009 .

[16]  Andrew D. Johnson,et al.  Genome-wide association study of blood pressure and hypertension , 2009, Nature Genetics.

[17]  Taesung Park,et al.  A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits , 2009, Nature Genetics.

[18]  May E. Montasser,et al.  Gene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican–Americans , 2009, Journal of hypertension.

[19]  D. Moller,et al.  Fibroblast growth factor 21 corrects obesity in mice. , 2008, Endocrinology.

[20]  L. Alcocer,et al.  Review: Hypertension, a health economics perspective , 2008, Therapeutic advances in cardiovascular disease.

[21]  C. Stehouwer,et al.  Microvascular dysfunction in obesity: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. , 2007, Physiology.

[22]  Yun-Fei Chen,et al.  The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. , 2007, Endocrinology.

[23]  J. Frisbee.  Hypertension‐Independent Microvascular Rarefaction in the Obese Zucker Rat Model of the Metabolic Syndrome , 2005, Microcirculation.

[24]  N. Zakopoulos,et al.  Impact of Obesity on 24-Hour Ambulatory Blood Pressure and Hypertension , 2005, Hypertension.

[25]  K. Reynolds,et al.  Global burden of hypertension: analysis of worldwide data , 2005, The Lancet.

[26]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[27]  Jing Chen,et al.  Geographic variations in the prevalence, awareness, treatment and control of hypertension in China , 2003, Journal of hypertension.

[28]  S. Maxwell,et al.  Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. , 2001, Journal of cell science.

[29]  D. Bates,et al.  Mixed-Effects Models in S and S-PLUS , 2001 .

[30]  K. Donato,et al.  Body mass index and the prevalence of hypertension and dyslipidemia. , 2000, Obesity research.

[31]  Mark D. Huffman,et al.  Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association. , 2013, Circulation.

[32]  E. Urbina,et al.  Korotkoff sound versus oscillometric cuff sphygmomanometers: comparison between auscultatory and DynaPulse blood pressure measurements. , 2011, Journal of the American Society of Hypertension : JASH.

[33]  A C Shore,et al.  Microvascular correlates of blood pressure, plasma glucose, and insulin resistance in health. , 2002, Cardiovascular research.

[34]  D. French,et al.  Printed in U.S.A. Copyright © 2002 by The Endocrine Society Transgenic Mice Expressing Human Fibroblast Growth Factor-19 Display Increased Metabolic Rate and Decreased Adiposity , 2022 .