Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with regulation of blood pressure
Abstract
Introduction: In spite nearly 40% of the variability in blood pressure can be explained by genetic factors, the identification of genes associated to essential high blood pressure is difficult in populations where individuals have different genetic precedents; in these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease.
Objectives: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide.
Methodology: A sample of 552 unrelated individuals was studied through analysis of Restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure.
Results: 38 Haplotypes were identified, with GCCTG4b as the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and genetic structure of populations was not evidenced (FST = 0,0038).
Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium, this indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies
Authors
Downloads
Keywords
- High blood pressure essence
- Complex disease
- GRK4
- eNOS
- Polymorphisms
- Populations genetics.
References
Hopkins PN, Hunt SC. Genetics of hypertension. Genet Med. 2003; 5: 413-29.
Premont RT, Macrae AD, Stoffel RH, Chung N, Pitcher JA, Am¬brose C, et al. Characterization of the G Protein-coupled Receptor Kinase GRK4. Identification of four splice variants. The Journal of Biological Chemistry. 1996; 271: 6403–410.
Hingorani AD. Endothelial Nitric Oxide Synthase Polymor¬phisms and Hypertension. Current Hypertension Reports. 2003; 5: 19–25.
Bautista LE. Inflammation, endothelial dysfunction, and the risk of high blood pressure: Epidemiologic and biological eviden¬ce. J Hum Hypertens. 2003; 17: 223-30.
Casas JP, Cavalleri GL, Bautista LE, Smeeth L, Humphries SE, Hingorani AD. Endothelial Nitric Oxide Synthase Gene Polymor¬phisms and Cardiovascular Disease: A HuGE Review. Am J Epi¬demiol. 2006; 64: 921-35.
Marchini J, Cardon LR, Phillips MS, Donnelly P. The effects of human population structure on large genetic association studies. Nat Genet. 2004; 36: 512-17.
Marroni A, Metzger I, Souza-Costa D, Nagassaki S, Sandrim V, Correa R, et al. Consistent interethnic differences in the distribu¬tion of clinically relevant endothelial nitric oxide synthase genetic polymorphisms. Nitric Oxide. 2005; 12: 177–82.
Iniesta R, Guinó E, Moreno V. Análisis estadístico de polimor¬fismos genéticos en estudios epidemiológicos. Gac Sanit. 2005; 19: 333-41.
Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000; 155: 945-59.
Bengra C, Mifflin TE, Khripin Y, Manunta P, Williams SM, Jose PA, et al. Genotyping of Essential Hypertension Single-Nu¬cleotide Polymorphisms by a Homogeneous PCR Method with Universal Energy Transfer Primers. Clinical Chemistry. 2002; 48: 2131–140.
Speirs HJ, K Katyk, Kumar NN, Benjafield AV, Wang WY, Mo¬rris BJ. Association of G-protein-coupled receptor kinase 4 haplo¬types, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension. Journal of Hypertension. 2004; 22: 931-36.
Williams SM, Ritchie MD, Phillips JA, Dawsone E, Prince M, Dzhura E, et al. Multilocus Analysis of Hypertension: A Hierar¬chical Approach. Hum Hered. 2004; 57: 28–38.
Wang Y, Li B, Zhao W, Liu P, Zhao Q, Chen S, et al. Association study of G protein-coupled Receptor Kinasa 4 gene variants with essential hypertension in Northern Han Chinese. Annals of Hu¬man Genetics. 2006; 70: 1-6.
Valverde E, Cabrero C, Cao R, Rodríguez-Calvo MS, Díez A, Barros F, et al. Population genetics of three VNTR polymorphisms in two different Spanish populations. International Journal of Le¬gal Medicine. 1993; 105: 251-56.
Serrano NC, Díaz LA, Casas JP, Hingorani AD, Moreno de Lucca D, Páez MC. Frequency of eNOS polymorphisms in the Co¬lombian general population. BMC genetics. 2010; 11: 54.
Kwok S, Chang SY, Sninsky JJ, Wang A. A guide to the de¬sign and use of mismatched and degenerate primers. Genome Re¬search. 1994; 3: 39-47.
Serrano N, Casas J, Diaz L, Paez C. Endothelial NO Synthase Genotype and Risk of Preeclampsia A Multicenter Case-Control Study. Hypertension. 2004; 44: 702-07.
Dean AG, Arner TG, Sunki GG, Friedman R, Lantiga M, San
gam S, et al. Epi Inf version 3.5.1, a database and statistics program for public health professionals. Centers for Disease Control and Prevention, Atlanta. 2002.
Peakall R, Smouse PE. GENALEX 6: genetic analysis in Excel. Population genetic software for teaching and research. Molecular Ecology Notes. 2006; 6: 288-95.
Excoffier L, Laval G, Schneider. Arlequin ver. 3.5: Anintegrated software package for population genetics data analysis. Evolutio¬nary Bioinformatics Online. 2005; 1: 47-50.
Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000; 155: 945-59.
Hartl DL, Clark AG. Organization of genetic variation: Linkage and Linkage disequilibrium. En: Principles of population genetics. Sunderland Massachusetts. Sinauer Associates Inc. 1997; 71-109.
Lohmueller K, Wong L, Mauney M, Jiang L, Felder R, Jose P, et al. Patterns of Genetic Variation in the Hypertension Candidate Gene GRK4: Ethnic Variation and Haplotype Structure. Annals of Human Genetics. 2005; 70: 27–41.
Hincapié ML, Gil AM, Pico AL, Gusmão L, Rondon F, Castillo A. Análisis de la estructura genética en una muestra poblacional de Bucaramanga, departamento de Santander. Colombia Médica. 2009; 40: 361-72.
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use
