Hypertriglyceridemia associated with amino acid variation Asn985Tyr of the RP1 gene.
Factors predisposing to the phenotypic features of hypertriglyceridemia have not been clearly defined. Here we report an association between a missense coding region polymorphism Asn985Tyr in the retinitis pigmentosa 1 gene ( RP1) and plasma triglyceride (TG) levels in 332 adult individuals from an east-central area of Japan. Age and gender-adjusted levels of LDL-cholesterol, TG, and HDL-cholesterol were analyzed. When we separate the subjects into two genotypic groups regarding this amino acid variation, those who lack the 985-Asn allele (asparagine at residue 985) had significantly higher plasma TG levels than the others who had at least one 985-Asn allele (mean: 175.8 mg/dl vs 123.3 mg/dl; P=0.0006, Mann-Whitney test). Similarly, the former subjects had significantly lower HDL-cholesterol levels than the latter (mean: 48.0 mg/dl vs 53.8 mg/dl; P=0.038). Of the 280 individuals without a 985-Asn allele, approximately half of the individuals presented with hypertriglyceridemia, whereas only a quarter were hypertriglyceridemic among 52 individuals with the 985-Asn allele ( P=0.04). Although this SNP marker may itself be in linkage disequilibrium with other unexamined functional variants within this locus, our data suggest that genetic variation at the RP1 locus is one of the likely candidate determinants for plasma triglyceride and HDL-cholesterol metabolisms.
Fujita
Yuko
Y
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.|Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Ezura
Yoichi
Y
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
Emi
Mitsuru
M
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan. memi@nms.ac.jp.
Ono
Shuji
S
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
Takada
Daisuke
D
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.|Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Takahashi
Kaneo
K
Awa Medical Association Hospital, Chiba, Japan.
Uemura
Kouhei
K
Awa Medical Association Hospital, Chiba, Japan.
Iino
Yasuhiko
Y
Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Katayama
Yasuo
Y
Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Bujo
Hideaki
H
Department of Genome Research and Clinical Application, Chiba University Graduate School, Chiba, Japan.
Saito
Yasushi
Y
Department of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
D000368:Aged; D000483:Alleles; D000596:Amino Acids / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood
D000596:Amino Acids; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol