A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal τs) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.
Bibliographical noteFunding Information:
The HERITAGE Family Study is supported by the NHLBI through the following grants: HL45670 (C. Bouchard, PI), HL47323 (A.S. Leon, PI), HL47317 (D.C. Rao, PI), HL47327 (J.S. Skinner, PI), and HL47321 (J.H. Wilmore, PI). A.S. Leon is also support by NIH-funded University of Minnesota’s Clinical Research Center (M01 RR 00400) and partially by the Henry L. Taylor Professorship. C. Bouchard is partially funded by the MRC and Roche Canada Donald B. Brown Research Chair on Obesity. Thanks are expressed to all the co-principal investigators, investigators, co-investigators, local project coordinators, research assistants, laboratory technicians, and secretaries who are contributing to the study.
- Insulin resistance