Da. Wu et al., QUANTITATIVE TRAIT LOCUS MAPPING OF HUMAN BLOOD-PRESSURE TO A GENETICREGION AT OR NEAR THE LIPOPROTEIN-LIPASE GENE LOCUS ON CHROMOSOME 8P22, The Journal of clinical investigation, 97(9), 1996, pp. 2111-2118
Resistance to insulin-mediated glucose disposal is a common finding in
patients with non-insulin-dependent diabetes mellitus (NIDDM), as wel
l as in nondiabetic individuals with hypertension, In an effort to ide
ntify the generic loci responsible for variations in blood pressure in
individuals at increased risk of insulin resistance, we studied the d
istribution of blood pressure in 48 Taiwanese families with NIDDM and
conducted quantitative sib-pair linkage analysis with candidate loci f
or insulin resistance, lipid metabolism, and blood pressure control. W
e found no evidence for linkage of the angiotensin converting enzyme l
ocus on chromosome 17, nor the angiotensinogen and renin loci on chrom
osome 1, with either systolic or diastolic blood pressures. In contras
t, we obtained significant evidence for linkage of systolic blood pres
sure, but not diastolic blood pressure, to a genetic region at or near
the lipoprotein lipase (LPL) locus on the short arm of chromosome 8 (
P = 0.002, n = 125 sib-pairs, for the haplotype generated from two sim
ple sequence repeat markers within the LPL gene). Further strengthenin
g this linkage observation, two flanking marker loci for LPL locus, D8
S261 (9 cM telomeric to LPL locus) and D8S282 (3 cM centromeric to LPL
locus), also showed evidence for linkage with systolic blood pressure
(P = 0.02 and 0.0002 for D8S261 and D8S282, respectively). Two additi
onal centromeric markers (D8S133, 5 cM from LPL locus, and NEFL, 11 cM
from LPL locus) yielded significant P values of 0.01 and 0.001, respe
ctively. Allelic variation around the LPL gene locus accounted for as
much as 52-73% of the total interindividual variation in systolic bloo
d pressure levels in this data set. Thus, we have identified a genetic
locus at or near the LPL gene locus which contributes to the variatio
n of systolic blood pressure levels in nondiabetic family members at h
igh risk for insulin resistance and NIDDM.