title: The StuI polymorphism on exon 8 of the low density lipoprotein (LDL) receptor gene: prevalence and impact on serum lipid levels in an Asian cohort.
abstract: A single nucleotide (A-->G) substitution in codon 370 (exon 8) of the low density lipoprotein (LDL) receptor gene results in loss of a StuI restriction site and an amino acid change (Ala370-->Thr) in the translated protein. This biallelic polymorphism has been associated with significant variations in plasma lipid concentrations in several Caucasian populations. We investigated its prevalence and impact on lipid metabolism in 539 Singaporeans of Chinese, Malay and Indian descent. The average frequency of 0.003 for the Thr370 allele and heterozygosity of 0.0056 were 10- to 20-fold lower than those reported in Caucasians (range 0.075 to 0.107). Distribution of the genotypes satisfied the Hardy-Weinberg equilibrium (chi 2 = 0.004, P = 0.948). We also found ethnic variation in the allele frequencies of Thr370 among the three races studied (0.009 in Indians, 0.007 in Malays, and 0.003 in Chinese). However, this needs to be confirmed with larger numbers. No significant correlation between genotype and serum concentrations of total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol, LDL-cholesterol, lipoprotein(a), apolipoprotein A and apolipoprotein B was found in our study. This argues strongly against a major contribution or impact of this intragenic polymorphic locus on modulating the serum lipid profiles of the study subjects.
authors.affiliation: Department of Pathology, National University of Singapore, Singapore.
authors.forename: M L
authors.initials: ML
authors.lastname: Choong
authors.forename: S K
authors.initials: SK
authors.lastname: Sethi
authors.forename: E S
authors.initials: ES
authors.lastname: Koay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D012016:Reference Values; D012846:Singapore
chemical_list: D008055:Lipids; D011973:Receptors, LDL; C028868:AGGCCT-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific