Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations.
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.
Iijima
Hiroshi
H
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.
Emi
Mitsuru
M
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.
Wada
Manabu
M
Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.
Daimon
Makoto
M
Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata, 992-9585, Japan.
Toriyama
Sayumi
S
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.
Koyano
Satoru
S
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.
Sato
Hidenori
H
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.
Hopkins
Paul N
PN
Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
Hunt
Steven C
SC
Cardiovascular Genetics, Department of Internal Medicine, Cardiology Division, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kubota
Isao
I
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Kawata
Sumio
S
Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
Kato
Takeo
T
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.
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
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C504173:LIPC protein, human; D008074:Lipoproteins; D008049:Lipase