KOSEN 한인과학기술자네트워크

Polymorphism에 대한 논문을 첨부합니다. 혹시 mutation study내용은 NCBI의 OMIM에서 145750로 search해 보시면 아래와 같은 내용이 있는데 더 많은 자료를 Link를 통해 참고하실 수 있습니다. HYPERTRIGLYCERIDEMIA, FAMILIAL Gene map locus 21q11.2, 15q11.2-q13.1, 11q23, 8q11-q13 TEXT A number sign (#) is used with this entry because susceptibility to hypertriglyceridemia has been associated with mutation in the apolipoprotein A5 gene (APOA5; 606368) and the lipase I gene (LIPI; 609252), and with polymorphism in the RP1 gene (603937.0005). The phenotype is that of hyperlipoproteinemia IV (144600). Relatives of affected persons (ascertained in a study of survivors of coronary occlusion) were found to have normal cholesterol distribution and bimodal triglyceride distribution (Goldstein et al., 1973). Hypertriglyceridemia is not completely expressed in affected children. Namboodiri et al. (1977) studied a large kindred with a high frequency of cardiac illness and with hyperlipidemia. Triglycerides showed 75% of the 'variance accountable by genetic transmission' and cholesterol 52%. Whether the disorder in this kindred should be called hypertriglyceridemia or combined hyperlipidemia (144250) is not clear. The authors chose to call it hypertriglyceridemia. Hypertriglyceridemia gave a good fit to autosomal dominant inheritance, the minimal probability of misclassification being 9.3%. Linkage analysis with 27 markers showed a positive score only with pepsinogen (169700): lod of 0.73 at recombination fraction of 0.1. In a 59-year-old man with severe hypertriglyceridemia, Breckenridge et al. (1978) found deficiency of apolipoprotein C-II (an activator for lipoprotein lipase); see 207750. After transfusion of 1 unit of plasma the patient's triglycerides fell, within 1 day, from 1000 to 250 mg per deciliter and remained below preinfusion concentration for 6 days. In DNA studies that showed that the APOA1 gene and the APOC3 gene are in close physical linkage, Karathanasis et al. (1983) also showed that the 2 genes are 'convergently transcribed' and that the polymorphism reported by Rees et al. (1983) to be associated with hypertriglyceridemia may be due to a single basepair substitution in the 3-prime-noncoding region of apoC-III mRNA. Hypertriglyceridemia has many causes but, whatever its cause, there is evidence for its role as a coronary heart disease risk factor. Hypertriglyceridemia is commonly found in individuals with type II diabetes mellitus (125853). Several genetic bases for hypertriglyceridemia have been identified. A susceptibility locus for familial combined hyperlipidemia (HYPLIP1; 602491) was localized to 1q. Some mutations in the ABC1 gene (600046) caused Tangier disease (205400), whereas others caused a mild disorder called type II familial high density lipoprotein deficiency (604091); both are associated with hypertriglyceridemia. Duggirala et al. (2000) conducted a genomewide scan for susceptibility genes influencing plasma triglyceride (TG) levels in a Mexican-American population. They used both phenotypic and genotypic data from 418 individuals distributed across 27 low-income, extended Mexican-American families. For the analyses, TG values were log transformed (ln TG). After accounting for the effects of sex and sex-specific age terms, they found significant evidence for linkage (lod = 3.88) of ln TG levels to a genetic location between the markers GABRB3 (137192) located at 15q11.2 and D15S165 located at 15q12-q13.1. This putative locus explains 39.7 +/- 7% (P = 0.000012) of total phenotypic variation in ln TG levels. Some evidence for linkage to 2 different locations on chromosome 7 was found. The apolipoprotein A5 gene (APOA5; 606368) plays an important role in determining plasma triglyceride concentrations in humans. Kao et al. (2003) described a novel variant in APOA5, G553T (606368.0001), that is associated with hypertriglyceridemia. The variant results in substitution of cysteine for glycine-185. The minor allele frequencies were 0.042 and 0.27 (P less than 0.001) for Chinese control and hypertriglyceridemic patients, respectively. The serum triglyceride level was significantly different among the genotypic groups (G/G 92.5 +/- 37.8 mg/dl, G/T 106.6 +/- 34.8 mg/dl, T/T 183.0 mg/dl, P = 0.014) in control subjects. Multiple logistic regression revealed that individuals carrying the minor allele had age, gender, and BMI (body mass index)-adjusted odds ratio of 11.73 (95% confidence interval of 6.617-20.793; P less than 0.0001) for developing hypertriglyceridemia in comparison to individuals without that allele. Wen et al. (2003) identified 2 Caucasian hypertriglyceridemic individuals who were heterozygous for a G-to-A transition at nucleotide 164 of the LIPI gene, resulting in substitution of tyrosine for a conserved cysteine at codon 55 (C55Y; 609252.0001). They identified 2 other coding SNPs that were associated with variation in plasma HDL cholesterol in independent normolipidemic populations. >familial hypertriglyceridemai환자의 경우 LDL, APO-CII protein의 결핍이 주원인으로 알려져 있습니다. 이러한 단백질 결핍시 유전자 이상(single nucleotide polymorphorism)에 대한 자료 부탁드립니다.