title: Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations.
abstract: Hepatic lipase (HL) plays a major role in the regulation of plasma lipids. Several groups seeking to find association between the gene encoding HL (LIPC) and plasma concentrations of high-density lipoprotein cholesterol (HDLc) using various methods and populations have reported conflicting results. We have approached the problem of demonstrating a relationship between the LIPC locus and HDLc by means of haplotype association using four single nucleotide polymorphisms (SNPs) (rs12594375G/A, rs8023503C/T, rs4775047C/T, and rs11634134T/A) located in intron 1 of the LIPC gene in two independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively. Significant association between hyperalphalipoproteinemia and a specific haplotype in this intron was detected in both populations. When HDLc levels among the three haplotypic categories were analyzed [haplotype rs8023503C/rs12594375G (haplotype-1; H1) homozygotes (H1H1), haplotype rs8023503T/rs12594375A (haplotype-2; H2) homozygotes (H2H2), and heterozygotes (H1H2)], HDLc levels were lowest among H1H1 [mean +/- standard error (SE) = 58.4 +/- 0.4 mg/dl], highest among H2H2 (62.5 +/- 0.8 mg/dl), and intermediate among H1H2 (59.2 +/- 0.4 mg/dl) (P = 0.00011), indicating that H2 haplotype elevates plasma HDLc levels. This association was validated in the second population (n = 1,638) (P = 0.00070). The results provide convincing evidence that the LIPC locus influences HDL metabolism.
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.|HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan. memi@a.toshima.ne.jp.|HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan. memi@a.toshima.ne.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Wada
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.|HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan.
authors.forename: Sayumi
authors.initials: S
authors.lastname: Toriyama
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.|HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyano
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.|HuBit Genomix Research Institute, 2-19, Hayabusa-cho, Chiyoda-ku, Tokyo, 102-0092, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.affiliation: Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan. tkato@med.id.yamagata-u.ac.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
mesh_terms: D000704:Analysis of Variance; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005091:Exons; D005787:Gene Frequency; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D007438:Introns; D008049:Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D020641:Polymorphism, Single Nucleotide
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C504173:LIPC protein, human; D008074:Lipoproteins; D008049:Lipase