Linkage analysis with candidate genes: the Taiwan young-onset hypertension genetic study

Abstract

A genetic linkage study of young-onset hypertension was performed on data from 59 nucleus families of Han Chinese residing in Taiwan. Thirty seven microsatellite markers near 18 hypertension candidate genes were genotyped. In a nonparametric identity-by-descent sibpair analysis, a positive linkage signal (defined as P<0.05) was found for four microsatellite markers, viz., D1S1612 (P=0.0162), D1S547 (P=0.0263), D8S 1145 (P= 0.0284), and D17S2193 (P=0.0256), which were located near genes for atrial natriuretic peptide (NPPA)/glucose transporter 5 (SLC2A5), angiotensinogen (AGT), lipoprotein lipase (LPL), and angiotensin-conveting enzyme (DCP1), respectively. Marker D5S1480 located near beta-2-adrenergic receptor (ADRB2) had a borderline P value (P=0.0785) for the positive signal. Comprehensive genotyping with further markers in these regions is underway to confirm whether these genes are linked to young-onset hypertension.

Variation near the Region of the Lipoprotein Lipase Gene and Hypertension or Blood Pressure Levels in Chinese.

“…Lipid metabolism is considered to be an important pathway of BP control (2). Although the way in which LPL is involved in the development of hypertension is not apparent, hypertension has been found to occur more often than expected in families with familial combined hyperlipidemia.…”

“…Although the way in which LPL is involved in the development of hypertension is not apparent, hypertension has been found to occur more often than expected in families with familial combined hyperlipidemia. Membrane ion transport, which has been related to hypertension, can be altered by lipid abnormalities and could have some involvement in the mechanisms that relate high triglyceride levels and hypertension (2). Another possible pathophysiological mechanism would involve the ability of elevated triglyceride to induce hyperinsulinemia, which could lead to hypertension through its effects on renal hemodynamics, sodium reabsorption and retention, and vascular hypertrophy (16).…”

“…In a quantitative sib pair linkage analysis in a Taiwanese population, BP was shown to be strongly linked to the LPL gene (7). Another genetic linkage study of young-onset hypertension in Taiwan suggested positive linkage between the marker D8S1145 near the LPL gene and hypertension (2). Zhu et al similarly showed that the LPL gene could be linked to EH in 95 Chinese families (8).…”

“…EH is frequently associated with serum lipid abnormalities, and has been found to occur more often than expected in families with familial combined hyperlipidemia (2). This suggests that there may be common underlying genetic determinants between BP regulation and lipid metabolism.…”

“…To date, only a few studies have explored the relation between the genetic variants near or in the LPL gene and BP variation. Positive linkage or association has been described in some studies, which indicate that the LPL gene may be an important candidate for affecting the risk of EH or BP variation (1,2,7,8).…”