IGF1 Gene Is Associated With Triglyceride Levels In Subjects With Family History Of Hypertension From The SAPPHIRe And TWB Projects

Chromosome 12q23-q24 has been linked to triglyceride (TG) levels by previous linkage studies, and it contains the Insulin-like growth factor 1 (IGF1) gene. We investigated the association between IGF1 and TG levels using two independent samples collected in Taiwan. First, based on 954 siblings in 397 families from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe), we found that rs978458 was associated with TG levels (β = -0.049, p = 0.0043) under a recessive genetic model. Specifically, subjects carrying the homozygous genotype of the minor allele had lower TG levels, compared with other subjects. Then, a series of stratification analyses in a large sample of 13,193 unrelated subjects from the Taiwan biobank (TWB) project showed that this association appeared in subjects with a family history (FH) of hypertension (β = -0.045, p = 0.0000034), but not in subjects without such an FH. A re-examination of the SAPPHIRe sample confirmed that this association appeared in subjects with an FH of hypertension (β = -0.068, p = 0.0025), but not in subjects without an FH. The successful replication in two independent samples indicated that IGF1 is associated with TG levels in subjects with an FH of hypertension in Taiwan.

[1]  Ž. Reiner.  Hypertriglyceridaemia and risk of coronary artery disease , 2017, Nature Reviews Cardiology.

[2]  R. Hegele,et al.  Genetics of Triglycerides and the Risk of Atherosclerosis , 2017, Current Atherosclerosis Reports.

[3]  Sanghoon Moon,et al.  Association analyses of East Asian individuals and trans‐ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels , 2017, Human molecular genetics.

[4]  Chen-Yang Shen,et al.  Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project. , 2016, Human molecular genetics.

[5]  M. Budoff.  Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease. , 2016, The American journal of cardiology.

[6]  D. Rader,et al.  Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics. , 2016, Trends in molecular medicine.

[7]  Marcelo P. Segura-Lepe,et al.  Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels , 2016, Journal of Medical Genetics.

[8]  R. Jayawardena,et al.  The influence of family history of Hypertension on disease prevalence and associated metabolic risk factors among Sri Lankan adults , 2015, BMC Public Health.

[9]  Sara M. Willems,et al.  The impact of low-frequency and rare variants on lipid levels , 2015, Nature Genetics.

[10]  Jie Cao,et al.  Genome-wide linkage and positional association analyses identify associations of novel AFF3 and NTM genes with triglycerides: the GenSalt study. , 2015, Journal of genetics and genomics = Yi chuan xue bao.

[11]  Markus Perola,et al.  Amerindian-specific regions under positive selection harbour new lipid variants in Latinos , 2014, Nature Communications.

[12]  Tanya M. Teslovich,et al.  Discovery and refinement of loci associated with lipid levels , 2013, Nature Genetics.

[13]  Xiaofeng Zhu,et al.  ARTICLE Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations , 2022 .

[14]  P. Lips,et al.  Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study. , 2013, European journal of endocrinology.

[15]  P. Sifianou,et al.  Cord blood triglycerides are associated with IGF-I levels and contribute to the identification of growth-restricted neonates. , 2012, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[16]  F. Hadaegh,et al.  Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women , 2012, Journal of Human Hypertension.

[17]  Tanya M. Teslovich,et al.  Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids , 2010, Nature.

[18]  K. Jamrozik,et al.  IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men. , 2010, European journal of endocrinology.

[19]  R. Duggirala,et al.  Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study , 2009, Diabetes.

[20]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[21]  N. Risch,et al.  Genome-wide linkage analysis of lipids in nondiabetic Chinese and Japanese from the SAPPHIRe family study. , 2006, American journal of hypertension.

[22]  N. Martin,et al.  Genome-wide linkage scan for loci influencing plasma triglycerides. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[23]  C. Bouchard,et al.  Pleiotropic QTL on Chromosome 12q23–q24 Influences Triglyceride and High-Density Lipoprotein Cholesterol Levels: The HERITAGE Family Study , 2006, Human biology.

[24]  D. S. Montgomery,et al.  Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemias⃞s⃞ The online version of this article (available at http://www.jlr.org) contains an additional four figures. Published, JLR Papers in Press, August 1, 2005. DOI 10.1194/j , 2005, Journal of Lipid Research.

[25]  A. Malhotra,et al.  Analysis of quantitative lipid traits in the genetics of NIDDM (GENNID) study. , 2005, Diabetes.

[26]  C. Dong,et al.  A genome scan for serum triglyceride in obese nuclear families Published, JLR Papers in Press, December 16, 2004. DOI 10.1194/jlr.M400391-JLR200 , 2005, Journal of Lipid Research.

[27]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[28]  T. Hansen,et al.  A common polymorphism in the promoter of the IGF-I gene associates with increased fasting serum triglyceride levels in glucose-tolerant subjects. , 2004, Clinical biochemistry.

[29]  T. Quertermous,et al.  Physical Inactivity is an Important Lifestyle Determinant of Insulin Resistance in Hypertensive Patients , 2004, Blood pressure.

[30]  John D. Storey,et al.  Statistical significance for genomewide studies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. McPeek,et al.  Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by homozygosity-by-descent mapping in a large Hutterite pedigree. , 2003, Human molecular genetics.

[32]  S. Hasstedt,et al.  Quantitative trait linkage analysis of lipid-related traits in familial type 2 diabetes: evidence for linkage of triglyceride levels to chromosome 19q. , 2002, Diabetes.

[33]  R. Olshen,et al.  Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations. , 2000, American journal of hypertension.

[34]  P. O'Connell,et al.  A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans. , 2000, American journal of human genetics.

[35]  J D Terwilliger,et al.  Genomewide scan for familial combined hyperlipidemia genes in finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels. , 1999, American journal of human genetics.

[36]  J. Hubacek,et al.  Genetic predisposition of human plasma triglyceride concentrations. , 2015, Physiological research.