Lipoprotein lipase gene is linked and associated with hypertension in Taiwan young-onset hypertension genetic study.
Hypertriglyceridemia has been extensively associated with hypertension. However, the mechanism behind it is poorly understood. A positive linkage signal between Lipoprotein lipase (LPL) and young-onset hypertension has been identified by us as the strongest among 18 candidate genes. Here we report our fine mapping works with seven microsatellite markers flanking LPL, sequencing results for its promoter and exons, and an extended association study with the identified single nucleotide polymorphisms(SNP). First, using data from 213 individuals in 59 nuclear families of young-onset hypertension, multipoint analysis revealed a NPL score of 3.02 for the LPL (GZ-14/GZ-15) marker in intron 6. LPL marker (p < 10(-12)) and the haplotypes containing its allele 1 (p < 0.0001) were also significantly associated with young hypertension by transmission disequilibrium test. In-depth sequencing revealed no mutation in promoter and exon regions, except two cSNP: 7754C--> A (C/A: 0.91/0.09), a silent mutation in exon 8 and S447X (C/G: 0.92/0.08), a stop codon mutation in exon 9. Other 11 cSNPs documented in NCBI GenBank are absent in our sample. Constructed from the above 2 cSNPs, haplotype AC showed a moderate TDT association with elevated triglyceride (p = 0.02) and with hypertension and elevated triglyceride combined (p = 0.06). Again, in an extended case-control study, a significant association was found between S447X and patients with persistent hypertension and elevated triglyceride (p = 0.02). We conclude that LPL variants may play a causal role in the development of hypertension in Taiwan Han Chinese. The moderate association with SNP haplotype suggests that other regulatory LPL variant may exist.
Chen
Pei
P
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Jou
Yuh-Shan
YS
Fann
Cathy S J
CS
Chen
Jaw-Wen
JW
Wu
Sheng-Yeu
SY
Pan
Wen-Harn
WH
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001794:Blood Pressure; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005091:Exons; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology*; D015810:Linkage Disequilibrium; D008055:Lipids; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013624:Taiwan; D014280:Triglycerides / Q000378:metabolism
D008055:Lipids; D014280:Triglycerides; D008071:Lipoprotein Lipase