BACKGROUND: Altered diastolic filling is an important contributor to several cardiovascular disorders. Multiple lines of evidence suggest a genetic contribution to left ventricular (LV) diastolic filling; however, chromosomal locations harboring genes involved in impaired LV diastolic filling have not been reported. The aim of this study was to identify chromosomal regions contributing to variation of LV transmitral early and late peak filling velocities (E and A velocities), Doppler echocardiographic measures of LV diastolic filling. METHODS: We adjusted E and A velocities for age, age squared, heart rate, body mass index, systolic blood pressure, field center, and antihypertensive medication in sex- and ethnicity-specific linear regression models. Standardized residuals were calculated and used in multipoint variance components linkage analysis (GENEHUNTER). Anonymous markers (Cooperative Human Linkage Center set 8) were available for 167 white hypertensive sibships (397 subjects, mean age 60 years) and 182 African American (393 subjects, mean age 52 years) hypertensive sibships. RESULTS: For E velocity, linkage was detected on chromosome 5 at 133.6 centimorgan (cM) in African Americans (logarithm of the odds [LOD] = 4.13), and suggestive linkage (LOD >1.9) was observed for regions on chromosome 10 (80.8 cM) and chromosome 20 (1.5 cM). For A velocity, suggestive linkage was found for chromosome 12 (GATA85A04) in whites and for chromosome 8 (122.9 cM) in African Americans. Genes contained in and around the linked region are important candidates for diastolic filling (calcium-modulating cyclophilin ligand [5q23], alpha-1B adrenergic receptor [5q23-32]). CONCLUSION: Significant linkage was detected for LV early diastolic peak filling velocity on chromosome 5 in African Americans, indicating that a genomic region may contribute to interindividual variation in LV diastolic filling.
BACKGROUND: Altered diastolic filling is an important contributor to several cardiovascular disorders. Multiple lines of evidence suggest a genetic contribution to left ventricular (LV) diastolic filling; however, chromosomal locations harboring genes involved in impaired LV diastolic filling have not been reported. The aim of this study was to identify chromosomal regions contributing to variation of LV transmitral early and late peak filling velocities (E and A velocities), Doppler echocardiographic measures of LV diastolic filling. METHODS: We adjusted E and A velocities for age, age squared, heart rate, body mass index, systolic blood pressure, field center, and antihypertensive medication in sex- and ethnicity-specific linear regression models. Standardized residuals were calculated and used in multipoint variance components linkage analysis (GENEHUNTER). Anonymous markers (Cooperative Human Linkage Center set 8) were available for 167 white hypertensive sibships (397 subjects, mean age 60 years) and 182 African American (393 subjects, mean age 52 years) hypertensive sibships. RESULTS: For E velocity, linkage was detected on chromosome 5 at 133.6 centimorgan (cM) in African Americans (logarithm of the odds [LOD] = 4.13), and suggestive linkage (LOD >1.9) was observed for regions on chromosome 10 (80.8 cM) and chromosome 20 (1.5 cM). For A velocity, suggestive linkage was found for chromosome 12 (GATA85A04) in whites and for chromosome 8 (122.9 cM) in African Americans. Genes contained in and around the linked region are important candidates for diastolic filling (calcium-modulating cyclophilin ligand [5q23], alpha-1B adrenergic receptor [5q23-32]). CONCLUSION: Significant linkage was detected for LV early diastolic peak filling velocity on chromosome 5 in African Americans, indicating that a genomic region may contribute to interindividual variation in LV diastolic filling.
Authors: Ervin R Fox; Kathy L Klos; Alan D Penman; George J Blair; Benjamin D Blossom; Donna Arnett; Richard B Devereux; Tandaw Samdarshi; Eric Boerwinkle; Thomas H Mosley Journal: Am J Hypertens Date: 2010-05-06 Impact factor: 2.689
Authors: Tandaw E Samdarshi; Herman A Taylor; Derrick Q Edwards; Philip R Liebson; Daniel F Sarpong; Satya S Shreenivas; George Howard; Robert J Garrison; Ervin R Fox Journal: Am Heart J Date: 2009-08 Impact factor: 4.749
Authors: Kiran K Khush; Sanjiv J Shah; Bryan Ristow; Teresa De Marco; Mary A Whooley; Nelson B Schiller Journal: J Am Soc Echocardiogr Date: 2007-06-25 Impact factor: 5.251
Authors: Pinchia Huang; Aldi T Kraja; Weihong Tang; Steven C Hunt; Kari E North; Cora E Lewis; Richard B Devereux; Giovanni de Simone; Donna K Arnett; Treva Rice; Dabeeru C Rao Journal: J Hypertens Date: 2008-07 Impact factor: 4.844
Authors: Anh N Do; Wei Zhao; Vinodh Srinivasasainagendra; Stella Aslibekyan; Hemant K Tiwari; Nita Limdi; Sanjiv J Shah; Degui Zhi; Uli Broeckel; C Charles Gu; D C Rao; Karen Schwander; Jennifer A Smith; Sharon L R Kardia; Donna K Arnett; Marguerite R Irvin Journal: J Hypertens Manag Date: 2017-07-20
Authors: Aldi T Kraja; Pinchia Huang; Weihong Tang; Steven C Hunt; Kari E North; Cora E Lewis; Richard B Devereux; Giovanni de Simone; Donna K Arnett; Treva Rice; D C Rao Journal: BMC Med Genet Date: 2008-11-27 Impact factor: 2.103