A DNA polymorphism of an apoprotein gene associates with the hypertriglyceridaemia of primary gout

Summary Genomic hybridization analysis has been used to investigate allelic frequencies of the genes coding for the four major apoproteins of high density lipoprotein (HDL); apoproteins AI, AII, CII and CIII, in a group of Caucasian subjects with primary gout. An uncommon allelic variant of the apoprotein CIII gene (the S2 allele) was significantly more common among the patients with gout (9/48, 19%) than among normouricaemic controls who were either randomly selected (1/41, 2%, P=0.03) or normotriglyceidaemic (0/33, 0%, P=0.013). Approximately 46% (22/48) of the subjects with gout were hypertriglyceridaemic (with a serum triglyceride >2.1 mmol/l). Of the 22 patients in this subgroup, 5 (23%) had the uncommon S1S2 genotype, which was also a significantly greater proportion than among the normotriglyceridaemic controls (P=0.015). These data suggest that the hypertriglyceridaemia associated with primary gout may have a genetic basis. In contrast, we found no differences in the frequencies of restriction fragment length polymorphisms of the genes for apoproteins AI, AII and CII.     

An apolipoprotein CIII marker associated with hypertriglyceridemia in Caucasians also confers increased risk in a west Japanese population

Polymorphisms and haplotypes at the adjacent apolipoprotein (apo) AI and CIII gene loci were investigated in 61 Japanese patients with triglycerides greater than 350 mg/dl and in 66 unrelated normolipidemic subjects. The polymorphic sites were the SstI site in the apoCIII 3 untranslated region, whose presence has previously been shown to be associated with hypertriglyceridemia (HTG) in Caucasians, and the MspI site in the third intron of the apoAI gene. The frequencies of the SstI minor allele (S2) were 0.48 in HTG patients and 0.25 in normolipidemic subjects (P < 0.00015). The frequencies of the MspI minor allele (M2) were 0.61 in HTG patients and 0.33 in normolipidemic subjects (P < 0.00001). The two polymorphic sites were in strong linkage disequilibrium, and maximum likelihood analysis supported the existence of three of the four possible haplotypes: S1-M1, S1-M2, and S2-M2. Since all S2 alleles were estimated to be present on M2-bearing chromosomes, the HTG-associated S2-M2 haplotype conferred the same approximate relative risk as the S2 allele alone when compared with the other two haplotypes (odds ratio 2.8). This study demonstrates that the S2 allele is a marker for HTG among west Japanese subjects as well as among Caucasians. The results suggest that S2-M2 chromosomes carry HTG susceptibility sequences that predate the separation of the Asian and Caucasian races.     

Frequency and effect of human apolipoprotein A-IV polymorphism on lipid and lipoprotein levels in an Icelandic population

Summary Human apolipoprotein A-IV (apo A-IV) exhibits a genetic polymorphism with two common alleles, A-IV¹ and A-IV², in Caucasian populations. We have investigated this polymorphism in the Icelandic population. The frequencies of the two alleles are significantly different from middel European populations with a higher frequency of the A-IV² allele (0.117 versus 0.077) occurring in Iceland. The alleles at the apo A-IV locus have significant effects on plasma high density lipoprotein cholesterol (HDL-C) and triglyceride levels. The average effect of the A-IV² allele is to raise HDL-C by 4.9 mg/dl and to lower triglyceride levels by 19.4mg/dl. We estimate that the genetic variability at the apo A-IV gene locus accounts for 3.1% of the total variability of HDL-C and for 2.8% of the total variability of triglycerides in the population from Iceland. This confirms and extends our previous observations on apo A-IV allele effects in Tyroleans in an independent population.     

The gender-specific apolipoprotein E genotype influence on the distribution of lipids and apolipoproteins in the population of Rochester, MN. I. Pleiotropic effects on means and variances.

The influences of the apolipoprotein E (Apo E) polymorphism and of gender on the distributions of plasma levels of total cholesterol (Total-C), 1n triglycerides (1n Trig), HDL cholesterol (HDL-C), and apolipoproteins AI (Apo AI), AII (Apo AII), 1n E (1nApo E), B (Apo B), CII (Apo CII), and 1n CIII (1nApo CIII) were studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Apo E genotypes influenced both phenotypic level and intragenotype phenotypic variability. The mean levels of six of the nine traits were influenced significantly by Apo E genotype. Intragenotype variability in eight of the nine traits was significantly different among Apo E genotypes. These effects were estimated separately in males and females. The contribution of allelic variation in the Apo E gene to the definition of the multivariate mena and variance of the lipid and apolipoprotein hyperspace was evaluated. These findings were used to demonstrate how heterogeneity of risk-factor-trait variance among genotype/gender-specific subgroups of the population at large may influence the evaluation of risk of coronary artery disease.     

Novel alleles of 31-bp VNTR polymorphism in the human cystathionine β-synthase (<Emphasis Type="Italic">CBS</Emphasis>) gene were detected in healthy Asians

A 31-bp variable number of tandem repeats (VNTR) polymorphism of the cystathionine β-synthase (CBS) gene was earlier reported in Caucasians of predominantly European descent and Indo-Caucasoid populations.We report here for the first time, the detection of allele 20, which was absent in Caucasian and Indo-Caucasoid populations, as a common allele present in Singaporean Chinese (6.25%), Indians (11.7%), and Malays (11.5%). Hence, allele 20 might be a specific allele for Asian populations. A relatively common allele 19 found in the Caucasian and Indo-Caucasoid populations (10.4%–10.6%) was absent in the Asian samples of this study. Therefore, allele 19 might be a specific allele for the Caucasian populations. A novel and rare allele 13, which was not reported before in the Caucasian and Indo-Caucasoid populations, was found in 0.5% of Singaporean Chinese as genotype 13/17 heterozygotes. The presence of alleles 13 and 20 were verified by DNA sequencing. There were five new genotypes (13/17, 16/20, 17/20, 18/20 and 20/20) not reported before in the Caucasian and Indo-Caucasoid populations, detected in this study. Nine genotypes (15/18, 16/18, 16/21, 17/19, 18/19, 18/21, 19/19, 19/21 and 21/21) which were present in the Caucasian and/or Indo-Caucasoid populations were absent in this study. Our results showed that CBS 31-bp VNTR polymorphism has a distinct genetic difference in allele and genotype frequencies between the European Caucasians, Indo-Caucasoid and Asian populations.     

Angiotensin I-converting enzyme (ACE): estimation of DNA haplotypes in unrelated individuals using denaturing gradient gel blots

The angiotensin I-converting enzyme (ACE) gene (17q23) is a candidate gene for essential hypertension and related diseases, but investigation of its role in human pathology is hampered by a lack of identified polymorphisms. Currently, a 287-bp insertion/deletion (I/D) RFLP in intron 16 represents the only one known. Additional polymorphisms for the ACE gene would make most families informative for linkage studies and would allow haplotypes to be assigned in association studies. To increase the information provided by the ACE gene, we used a sensitive screening technique, denaturing gradient gel electrophoresis (DGGE) blots, to identify polymorphisms and combined this with gene counting to identify haplotypes. Five independent polymorphisms, restriction fragment melting polymorphisms (RFMPs), were identified by four probes (encompassing half of the ACE cDNA) in digests produced by three restriction enzymes (DdeI, RsaI, and AluI). One RFMP has three alleles while the others have two alleles. In a sample of 67 unrelated control subjects, minor allele frequencies ranged from 0.12 to 0.49. A significant level of linkage disequilibrium was found for all pairs of markers. The four most informative RFMPs, taken in combination, define 24 potential haplotypes. Based on gene counting, 11 of the 24 are rare or nonexistent in this population, and the estimated heterozygosity of the remaining 13 haplotypes approaches 80%. Under these conditions for the ACE locus, phase-unknown genotypes could be assigned to haplotype pairs in unrelated subjects with reasonable certainty. Thus, using DGGE blot technique for identifying numerous DNA polymorphisms in a candidate locus, in combination with gene counting, one can often identify DNA haplotypes for both related and unrelated study subjects at a candidate locus. These markers in the ACE gene should be useful for clinical and epidemiologic studies of the role of ACE in human disease.     

haplotypes identified by DNA polymorphisms at the apolipoprotein A-1 and C-III loci and hypertriglyceridaemia

Summary A Japanese group comprising 40 hypertriglyceridaemic and 35 normolipidaemic subjects were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) at the A-1 and C-III gene loci. An Sst-1 polymorphism is located at the 3 end of the C-III gene and a Msp-1 polymorphism in the third intron of the A-1 gene. The polymorphic restriction sites are 3.8kb apart. The polymorphism with Sst-1 was present at allelic frequencies of 0.67 (S1 allele) and 0.33 (S2 allele), and the polymorphism with Msp-1 was present at allelic frequencies of 0.55 (M1 allele) and 0.45 (M2 allele). The alleles S1, S2, M1, and M2 are in linkage disequilibrium and three haplotypes were identified S1-M1, S1-M2, and S2-M2. Unlike the previously reported association of the S2 allele with hypertriglyceridaemia found in Caucasians there was no difference in the frequency of S2 allele between normolipidaemic and hyperlipidaemic Japanese. However one of the haplotypes S1-M2 was significantly increased in the hypertriglyceridaemic subjects (32% versus 11% P>0.025). Thus in Japanese there is an association with genotypes at this locus and hypertriglyceridaemia but with a different haplotype than in Caucasians.     

Apo E gene polymorphism on development of diabetic nephropathy

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.     

Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men

In this study we have analysed the apolipoprotein (Apo) E polymorphism and polymorphisms of the ApoB gene, including the ApoB/Xba I and ApoB/4311 diallelic polymorphisms and a hypervariable region (HVR) situated in the 3 region of the gene (ApoB/3HVR), in a sample of healthy male subjects from Taiyuan (northern People's Republic of China). In comparison to Caucasian populations, in the Chinese sample, the Xba I2 allele (presence of cutting site; frequency 6.1%; and 95% confidence interval, 3.3–8.9) and the long HVR alleles (9.4%; 6.0–12.8) were rare, whereas the ApoB/4311 (Ser) allele (70.8%; 65.4–76.2) and the 34-repeat allele of the HVR (HVR34; 62.4%; 56.8–68.0) were frequent. In subjects having none, one, or two HVR34 alleles, the mean levels of plasma triglycerides were 2.32±1.44 (SD), 1.45+0.74, and 1.75±1.07 g/l, respectively (P < 0.007). Similar trends were observed for very low density lipoprotein (VLDL) cholesterol, LpE:B, and LpCIII:B. The frequencies of the ApoE alleles were similar to those reported in other populations of Asian origin; E2 (7.4%; 4.2–10.6), E3 (84.4%; 80.2–88.6), and E4 (8.2%; 5.0–11.4). Individuals carrying the E2 allele had a lower mean level of ApoB than E33 individuals: 0.87±0.16 and 1.00±0.22 g/l, respectively (P < 0.007). Individuals carrying the E4 allele had higher levels of ApoE than E33 individuals: 0.140±0.084 and 0.094±0.052 g/l, respectively (P < 0.004); similar trends were observed for VLDL cholesterol, triglycerides, LpE:B, and LpCIII:B. The ApoB/ HVR34 and ApoE/E4 polymorphisms accounted for 10% to 15% of the variability of the plasma levels of VLDL cholesterol, ApoE, triglycerides, LpE:B, and LpCIII:B. Several lipid variables appeared to be favourably affected by specific forms of ApoB and ApoE that are particularly frequent in this Chinese population.     

Common variants within the interleukin 4 receptor α gene (IL4R) are associated with susceptibility to osteoarthritis

Primary osteoarthritis (OA) is a common late-onset arthritis that demonstrates a complex mode of transmittance with both joint-site and gender-specific heterogeneity. We have previously linkage-mapped an OA susceptibility locus to a 12-cM interval at chromosome 16p12.3-p12.1 in a cohort of 146 affected female sibling-pair families ascertained by total hip replacement (female-THR families), with a maximum multipoint LOD score of 1.7. Despite the low LOD score, we were encouraged to investigate this interval further following the report of a linkage to the same interval in an Icelandic pedigree with an early-onset form of hip OA. Using public databases, we searched the interval for plausible candidates and concluded that the gene encoding the interleukin 4 receptor chain (IL4R) was a particularly strong candidate based on its known role in cartilage homeostasis. We genotyped nine common single nucleotide polymorphisms (SNPs) from within IL4R, including six non-synonymous SNPs, in the 146 probands from our female-THR families (stage 1) and in an independent cohort of 310 female-THR cases (stage 2). We compared allele frequencies with those of 399 age-matched female controls. All individuals were UK Caucasians. The minor alleles of two SNPs demonstrated association in both stages, with the most significant association having a P-value of 0.004 with an odds ratio (OR) of 2.1. These two SNPs defined two associated SNP groups. Inheriting a minor SNP allele from both groups was a particular risk factor (OR=2.4, P=0.0008). Our data suggest that functional variants within the IL4R gene predispose to hip OA in Caucasian females.     

Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism

Heme oxygenase-1 (HO-1) acts in cytoprotection against oxidants and aromatic hydrocarbons in cigarette smoke. A (GT)_n dinucleotide repeat in the 5-flanking region of the human HO-1 gene (alias HMOX1) reduces HO-1 inducibility and shows length polymorphism, which is grouped into three classes: class S (<27 GT), class M (27–32 GT), and class L (33 GT) alleles. To investigate the correlation between the HO-1 gene polymorphism and the development of lung adenocarcinoma, we screened 151 Japanese patients with lung adenocarcinoma and 153 control subjects. Patients and control subjects were frequency-matched by age, gender, smoking history and proportion of chronic pulmonary emphysema. The proportion of class L allele frequencies, as well as that of genotypic frequencies in L allele carriers (LL, LM, and LS), were significantly higher in patients with lung adenocarcinoma than those of control subjects. The adjusted odds ratio (OR) for lung adenocarcinoma with class L allele vs non-L allele (M+S) was 1.6 [95% confidence interval (CI) 1.0–2.5, P=0.03] and that with L allele carriers vs. non-L allele carriers was 1.8 (95% CI 1.1–3.0, P=0.02). Furthermore, the risk of lung adenocaricinoma for L allele carriers versus non-L allele carriers was much increased in the group of male smokers (OR=3.3, 95% CI 1.5–7.4, P=0.004). However, in the female non-smokers, the proportion of L allele carriers did not differ between patients and control subjects (OR=0.93, 95% CI 0.4–2.0, P=0.85). These findings suggest that the large size of a (GT)_n repeat in the HO-1 gene promoter may be associated with the development of lung adenocarcinoma in Japanese male smokers.     

Haplotypes of the human apoprotein AI-CIII-AIV gene cluster in coronary atherosclerosis

Summary Restriction fragment length polymorphisms of the apoprotein AI-CIII-AIV gene cluster (on the long arm of chromosome 11) were investigated in a group of Caucasian survivors of myocardial infarction, using genomic hybridisation analysis. Four common haplotypes were identified at this locus, M1P1S1 (a), M2P1S1 (b), M1P2S1 (c), and M2P1S2 (d); where M1 and M2 are the common and uncommon alleles defined using the restriction enzyme MspI, P1 and P2 are the common and uncommon alleles defined by the enzyme PstI, and S1 and S2 are the common and uncommon alleles defined by the enzyme SstI. Seven genotype combinations were observed of approximate frequencies; a/a 0.70 (33/47), a/d 0.15 (7/47), a/b 0.04 (2/47), d/d 0.04 (2/47), a/c 0.02 (1/47), b/c 0.02 (1/47), and c/d 0.02 (1/47). In contrast the corresponding values for normotriglyceridaemic Caucasian controls, without a personal or family history of atherosclerotic heart disease were; 0.83 (40/48), 0.02 (1/48), 0.06 (3/48), 0, 0.04 (2/48), 0.04 (2/48), and 0. The relative incidence of the d haplotype, characterised by the presence of a cleavage site for the enzyme Sstl in the fourth exon of the ApoCIII gene was significantly higher in the patient group (P<0.01). However, because of the tight linkage between the polymorphic loci studied, it was not possible to identify haplotypes associated with any greater risk of premature atherosclerosis than when the SstI polymorphism was considered in isolation.     

High degree of genetic polymorphism in apolipoprotein(a) associated with plasma lipoprotein(a) levels in Japanese and Chinese populations

We have developed a sensitve, high-resolution method for the analysis of the apolipoprotein(a) [apo(a)] isoforms using sodium dodecyl sulfate (SDS)-agarose/ gradient polyacrylamide gel electrophoresis. In an analysis of the genetic polymorphism of apo(a) isoforms and their relationship with plasma lipoprotein(a) [Lp(a)] levels in Japanese and Chinese, this method identified 25 different apo(a) isoforms and detected one or two apo(a) isoforms in more than 99.5% of the individuals tested. The apparent molecular weights of the apo(a) isoforms ranged from 370 kDa to 950 kDa, and 22 of the 25 different apo(a) isoforns had a higher molecular weight than of apo B-100. Studies on Japanese families confirmed the autosomal codominant segregation of apo(a) isoforms and the existence of a null allele at the apo(a) locus. The observed frequency distribution of apo(a) isoform phenotypes fit the expectations of the Hardy-Weinberg equilibrium in both the Japanese and Chinese populations. Our data indicate the existence of at least 26 alleles, including a null allele, at the apo(a) locus. The frequency distribution patterns of the apo(a) isoform alleles in Japanese and Chinese were similar to each other and also similar to that of apo(a) gene sizes reported in Caucasian American individuals. The average heterozygosity at the apo(a) locus was 92% in Japanese and 93% in Chinese. A highly significant inverse correlation was observed between plasma Lp(a) levels and the size of apo(a) isoforms in both the Japanese (r=-0.677, P=0.0001) and the Chinese (r=-0.703, P=0.0001). A highly skewed distribution of Lp(a) concentrations towards lower levels in the Japanese population may be explained by high frequencies of alleles encoding large apo(a) isoforms and the null allele.     

Linkage of type I diabetes to 15q26 (IDDM3) in the Danish population

Affected sib pair and linkage disequilibrium analysis, intrafamilial and case-control association studies were performed on 81 Danish multiplex insulin-dependent diabetes mellitus (IDDM) families (382 individuals) and 82 healthy Danish controls. The results confirm the linkage of D15S107 to IDDM in these Danish IDDM families (P = 0.010). When these data are combined with those of previous studies, an even stronger case for linkage can be made (P = 0.0005). Our analyses show that the D15S107*130 allele provides increased susceptibility (P = 0.02, relative risk = 3.55) and that the D15S107 locus contributes up to 16% of the familial clustering of IDDM. The analysis of affected sib pairs suggests that HLA and D15S107 may possibly act independently of each other. Taken together with our previous findings, our results suggest that three causes of susceptibilities can be discerned in the IDDM patient population: (1) a major susceptibility caused by the HLA-DRB1 alleles; (2) a minor susceptibility caused by the joint action of HLA and other non-HLA gene(s); and (3) a minor susceptibility caused by non-HLA gene(s). Received: 18 March 1996 / Revised: 17 May 1996     

Allele frequency distributions of Apo B VNTR locus in Cukurova, Turkey

The highly polymorphic minisatellites contain a variable number of tandemly repeated (VNTR) DNA sequences. They are extremely useful and informative markers to study genetic variation among human populations. We have analysed the allele frequency distribution at the highly polymorphic apolipoprotein B (Apo B) VNTR locus in order to obtain the population data for the Cukurova region in Turkey by using the polymerase chain reaction and polyacrylamide gel electrophoresis. We observed 10 different alleles and 21 genotypes in a sample of 100 unrelated individuals. The allele frequencies ranged from 0.01 to 0.4, with an expected heterozygosity of 0.69 for the Apo B locus. Alleles 37 (frequency = 0.4) and 35 (frequency = 0.17) were the most common in the Cukurova population. There was a significant deviation from the Hardy-Weinberg equilibrium (HWE) for genotype frequencies (chi2 = 29.12; df = 1; p = 0.000). This study possesses novelty as it is the first DNA polymorphism study conducted at the Cukurova population using an Apo B minisatellite locus.     

Transferability of Simple Sequence Repeat (SSR) Markers Developed in <Emphasis Type="Italic">Litchi chinensis</Emphasis> to <Emphasis Type="Italic">Blighia sapida</Emphasis> (Sapindaceae)

Ackee (Blighia sapida, Sapindaceae) is a multipurpose fruit tree species of high economic importance, native to the Guinean forests of West Africa, and belongs to the same family as that of lychee (Litchi chinensis). In this study, a set of 12 primer pairs for simple sequence repeats (SSRs) previously developed for lychee has been evaluated for polymorphism in 16 ackee trees from different populations. Seven primer pairs have been found to be transferable, and four have revealed polymorphisms. However, the average number of alleles per locus has dropped from 4.9 for lychee to 3.7 for ackee. Characterization of the four polymorphic markers in 279 individuals belonging to14 different ackee populations from Benin has revealed that the numbers of alleles per locus range from two to 14 with a mean number of 5.8. The observed and expected heterozygosities range between 0.020 to 0.359 and 0.020 to 0.396, respectively.     

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and −1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction—restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.     

The Relationship between Gene Polymorphism and CRP Level in a Chinese Han Population

We investigated the relationships among the +1444C/T polymorphism in the C-reactive protein (CRP) gene and the concentration of CRP and the risk of coronary heart disease. Using polymerase chain reaction-restriction fragment length polymorphism, we analyzed the frequency distribution of genotypes and alleles of the +1444C/T polymorphism in samples from 128 patients with coronary heart disease (coronary stenosis more than 50%) and 119 unrelated normal individuals. The plasma levels of CRP and lipids in the subjects were also measured. The frequencies of the genotypes were CC 89.1%, CT 10.9%, and TT 0% in patients and CC 89.9%, CT 10.1%, and TT 0% in controls. The frequency of allele C was 94.5% in patients and 95.0% in controls, and allele T was 5.5% in patients and 5.1% in controls. The distribution of genotypes and alleles in the Chinese Han population was significantly different from that of the Caucasian population. There were no significant differences between frequencies of genotype and allele of controls and those of patients (P>0.05), but in controls the concentrations of CRP in the CC genotype subgroup were significantly higher than those in the CT genotype subgroup (P<0.05). This suggests that the +1444C/T variant in the CRP gene influences the basal CRP level in normal people. These findings imply that there may eventually be a need to establish genotype-specific risk thresholds of the CRP level.     

Analysis of Microsatellite DNA Polymorphisms in Rockfish Sebastes thompsoni and Application to Population Genetics Studies

Population differentiation and relationships among 6 natural rockfish populations collected from northern coastal seas around Japan were assayed using microsatellite DNA loci. Seven loci examined were polymorphic in all populations. The number of alleles per locus ranged from 6.7 to 9.3, and the average of observed and expected heterozygosity ranged from 0.63 to 0.68, and from 0.66 to 0.69, respectively. The observed genotype frequencies at each locus were almost in agreement with Hardy-Weinberg expectations with two exceptions (P < .05). The allele frequencies of 16 population pairs were significantly different (P < .05). Genetic distance (D _A ) between 6 populations ranged from 0.03 to 0.08. According to a neighbor-joining tree generated from the D _A values, the 6 populations fell into 3 clusters. These clusters were correlated with the geographical positions of each population; larval dispersions due to water current were also found to have an effect on these results. Received May 2, 2000; accepted July 17, 2000.