Refinement and role of the diagnosis of Gilbert disease with molecular biology

Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1). Recently, the genetic basis of GS has been identified in caucasian populations : it is related to the insertion of a dinucleotide (TA) in the promoter region of the UGT1A1 gene. In Asian populations, GS is due to missense mutations (either homozygous or heterozygous) in the coding sequence. The aim of this study was to develop a simple and rapid method to detect both genetic polymorphisms and mutations. This technique was performed (1) to explore unrelated unconjugated hyperbilirubinemia; (2) to evaluate the frequency of GS in a population of 97 healthy caucasian volunteers: 17% of them were homozygous for the TA7/TA7 polymorphism; (3) to determine the incidence of this syndrome in a population of 105 neonates with unconjugated hyperbilirubinemia. The incidence of GS (15%) was not significantly higher than it was in the control group. A correlation between GS genotype and neonatal jaundice was not established; (4) to seek a relationship between GS and preeclampsia with or without Hellp syndrome. The incidence in the Hellp syndrome group (n = 19) was 26%, two fold higher than in preeclampsia group (n = 22) and control group (n = 50) with only 14% and 13% respectively, (5) to start a study regarding the toxicity of irinotecan treatment in a population of homozygous children for the UGT1A1 polymorphism.     

Prevalence of uridine glucuronosyl transferase 1A1 (UGT1A1) mutations in Malay neonates with severe jaundice

A number of genetic risk factors have been implicated in the development of neonatal severe hyperbilirubinaemia. This includes mutations in the uridine glucoronosyl transferase 1A1 (UGT1A1) gene which is responsible for unconjugated hyperbilirubinemia in Gilbert's Syndrome. We studied the prevalence of UGT1A1 gene mutations in a group of Malay neonates to determine whether they are risk factors to severe neonatal jaundice. One hundred and twenty-five Malay neonates with severe hyperbilirubinemia were studied. Ninety-eight infants without severe hyperbilirubinaemia were randomly selected from healthy Malay term infants (controls). DNA from EDTA cord blood samples were examined for UGT1A1 mutations nt211G > A and nt247T > C using established Taqman SNP genotyping assays and the UGT1A1*28 variant was detected by the Agilent 2100 bioanalyzer. All samples were also screened for common Malay G6PD variants using established techniques. The frequency of UGT1A1 211G > A mutation is significantly higher in the severely hyperbilirubinemic group (13%) than the control group (4%; p = 0.015) and all the positive cases were heterozygous for the mutation. There was no significant difference in the frequency of UGT1A1*28 mutation between the severely hyperbilirubinemic (3.5%) and the control group (0.01%; p = 0.09). None of the neonates in both groups carried the nt247 T > C mutation. The prevalence of G6PD mutation was significantly higher in the severely jaundiced group than control (9% vs 4%; p = 0.04). In conclusion, nt 211 G > A alleles constitute at least 12% of UGT1A1 mutations underlying unconjugated hyperbilirubinemia and appears to be a significant independent risk factor associated with severe neonatal hyperbilirubinemia in the Malay newborns.     

Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype

Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. Lesions in the gene encoding bilirubin-UGT(1), lead to complete or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type-1 (CN-1) and type 2 (CN-2), respectively. Inactivation of the enzyme leads to accumulation of unconjugated bilirubin in the serum. Severe hyperbilirubinemia seen in CN-1 can cause bilirubin encephalopathy (kernicterus). Kernicterus can be fatal or may leave behind permanent neurological sequelae. Here, we have compiled more than 50 genetic lesions of UGT1A1 that cause CN-1 (including 9 novel mutations) or CN-2 (including 3 novel mutations) and have presented a correlation of structure to function of UGT1A1. In contrast to Crigler-Najjar syndromes, Gilbert syndrome is a common inherited condition characterized by mild hyperbilirubinemia. An insertional mutation of the TATAA element upstream to UGT1A1 results in a reduced level of expression of the gene. Homozygosity for the variant promoter is required for Gilbert syndrome, but not sufficient for manifestation of hyperbilirubinemia, which is partly dependent on the rate of bilirubin production. Several structural mutations of UGT1A1, for example, a G71R substitution, have been reported to cause mild reduction of UGT activity toward bilirubin, resulting in mild hyperbilirubinemia, consistent with Gilbert syndrome. When the normal allele of a heterozygote carrier for a Crigler-Najjar type structural mutation contains a Gilbert type promoter, intermediate levels of hyperbilirubinemia, consistent with the diagnosis of CN-2, may be observed.     

Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates

We performed DNA analysis on cord blood samples of 128 Chinese male neonates diagnosed as G6PD deficiency in Hospital Universiti Kebangsaan Malaysia by a combination PCR-restriction enzyme digest technique, Single Stranded Conformation Polymorphism analysis and DNA sequencing. We found 10 different G6PD-deficient mutations exist. The two commonest alleles were G6PD Canton 1376 G>T (42.3%) and Kaiping 1388 G>A (39.4%) followed by G6PD Gaohe 592 G>A (7.0%), Chinese-5 1024 C>T, Nankang 517 T>C (1.5%), Mahidol 487 G>A (1.6%), Chatham 1003 G>T (0.8%), Union 1360 C>T (0.8%), Viangchan 871 G>A (0.8%) and Quing Yang 392 G>T (0.8%). Sixty eight percent (88/125) neonates in this study had neonatal jaundice and 29.7% developed hyperbilirubinemia >250 micromol/l. The incidence of hyperbilirubinemia >250 micromol/l was higher in G6PD Kaiping (43.8%) than G6PD Canton (22%) (p< 0.05). There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean duration of phototherapy between the two major variants. None of the 88 neonates required exchange transfusion. In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays.     

Glucose‐6‐phosphate dehydrogenase (G6PD) variants in Malaysian Chinese

We screened 38 G6PD‐deficient male Chinese neonates for known G6PD mutations using established PCR‐based techniques. We found 50.0% (19 of 38) were mutation 1376G>T, 34.2% (13 of 38) were mutation 1388G>A, 5.2% (2 of 38 ) were mutation 95A>G and 2.2% (1 of 38) was mutation 1024C>T. In 7% (3 of 38) of the cases the mutations remained uncharacterised. Sixty three percent (24 of 38) of the G6PD deficient neonates had neonatal jaundice with 28.9 % (11 of 38) developing moderate to severe hyperbilirubinemia . The group of neonates with 1388 mutation showed the highest incidence of moderate to severe hyperbilirubinemia requiring phototherapy and/or exchange transfusion respectively. Majority (70%) of the G6PD deficient neonates showed severe enzyme deficiency. However, there was no meaningful association between the level of enzyme activity and the severity of neonatal jaundice. In summary, four mutations account for more than 90% of the G6PD deficiency cases among the Chinese in Malaysia and the pattern of distribution of the molecular variants is similar to those found among the Chinese in Taiwan and southern mainland China. Our findings also suggest the possible association of nt 1388 mutation with severe neonatal jaundice. Hum Mutat 14:352, 1999. © 1999 Wiley‐Liss, Inc.     

Analysis of bilirubin uridine 5′-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II

Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic bilirubin uridine 5′-diphosphate (UDP)-glucuronosyltransferase activity. Recently, there has been progress in mutation analysis of patients with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from five unrelated families. The mutations found in this study were classified into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These mutations, which were detected in five patients from three unrelated families, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Trp) in exon 1. The third type, which was detected in one patient and was a new type of mutation combination, was composed of a homozygous insertion mutation of the TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1. Although the first and the second type of mutations are recessive, the third type appears to be dominant with incomplete penetrance, since the allele frequency of the insertion mutation of the TATAA element is very high (40%). Received: July 4, 1997 / Accepted: August 25, 1997     

酪酸梭菌活菌散剂在治疗新生儿高胆红素血症中的作用

目的 分析酪酸梭菌活菌散剂在治疗新生儿高胆红素血症中的作用。方法 选择2017年4月~2019年3月在我院诊治的200例高胆红素血症新生儿,采用随机数字表法分为对照组和观察组,各100例。对照组采用蓝光照射等对症治疗,观察组在对照组基础上采用酪酸梭菌活菌散剂治疗,比较两组临床治疗总有效率、治疗前、治疗1、3、5 d血清总胆红素水平、黄疸消退时间、不良反应发生率。结果 观察组治疗总有效率为95.00%,高于对照组的82.00%,差异有统计学意义（P＜0.05）;观察组治疗1、3、5 d血清总胆红素水平均低于对照组,差异有统计学意义（P＜0.05）;观察组黄疸消退时间为（4.71±1.80）d,短于对照组的（6.23±2.56）d,差异有统计学意义（P＜0.05）;观察组临床不良反应发生率为12.00%,低于对照组的28.00%,差异有统计学意义（P＜0.05）。结论 酪酸梭菌活菌散剂辅助治疗新生儿高胆红素血症疗效显著,可缩短黄疸消退时间,且不良反应少,用药安全可靠,值得临床应用。     

Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Malays

We performed DNA analysis using cord blood samples on 86 male Malay neonates diagnosed as G6PD deficiency in the National University of Malaysia Hospital by a combination of rapid PCR-based techniques, single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. We found 37.2% were 871G>A (G6PD Viangchan), 26.7% were nt 563 C>T (G6PD Mediterranean) and 15.1% were 487G>A (G6PD Mahidol) followed by 4.7% 1376G>T (G6PD Canton), 3.5% 383T>C (G6PD Vanua Lava), 3.5% 592C>T (G6PD Coimbra), 2.3% 1388G>A (G6PD Kaiping), 2.3% 1360C>T (G6PD Union), 2.3% 1003G>A (G6PD Chatham), 1.2% 131C>G (G6PD Orissa) and 1.2% 1361G>A (G6PD Andalus). Seventy-one (82.6%) of the 86 G6PD-deficient neonates had neonatal jaundice. Fifty seven (80%) of the 71 neonates with jaundice required phototherapy with only one neonate progressing to severe hyperbilirubinemia (serum bilirubin >340 micromol/l) requiring exchange transfusion. There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin level, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean number of days of phototherapy between the three common variants. In conclusion, the molecular defects of Malay G6PD deficiency is heterogeneous and G6PD Viangchan, Mahidol and Mediterranean account for at least 80% of the cases. Our findings support the observation that G6PD Viangchan and Mahidol are common Southeast Asian variants. Their presence in the Malays suggests a common ancestral origin with the Cambodians, Laotians and Thais. Our findings together with other preliminary data on the presence of the Mediterranean variant in this region provide evidence of strong Arab influence in the Malay Archipelago.     

喂养方式与新生儿高胆红素血症的关系

将229例足月健康新生儿(Apgar评分8～10分)按照喂养的方式分为母婴同室和混合喂养两组,观察在两种喂养方式下高胆红素血症的发病率和血清胆红素的水平。结果表明,两组新生儿的高胆红素血症发病率没有显著性差异,母婴同室的高胆红素血症发病率并没有高于混合喂养组,但母婴同室组的血清胆红素水平却明显低于混合组(P<0.02)。尤其在不明原因黄疸的新生儿中,两种喂养方式下的血清胆红素水平有非常显著的差异(P<0.001)。喂养方式在ABO血型不合、G-6-PD缺陷、母HBsAg阳性等因素组的新生儿高胆红素血症的发病率和血清胆红素水平中影响不大。母婴同室可降低新生儿血清胆红素水平,提高新生儿的机体状态。     

Combined in vitro and in silico analyses of FGFR1 variants: genotype-phenotype study in idiopathic hypogonadotropic hypogonadism

Fibroblast growth factor receptor 1 (FGFR1) is an idiopathic hypogonadotropic hypogonadism (IHH)-associated gene, mutated in approximately 10% of the patients with this condition. Through targeted gene sequencing of 153 males with IHH and 100 healthy controls, we identified 10 mutations in FGFR1 from IHH patients with a frequency of 5.9% in the Chinese population of central China. These included nine missense mutations(NM_023110.2, p.Gly687Arg, p.Ala608Asp, p.Gly348Glu, p.Asn296Ser, p.Gly226Asp, p.Arg209Cys, p.Gly97Arg, p.Val71Met, p.Gly70Arg) and a splicing mutation c.1430 + 1G > T. in vitro and in silico analyses of FGFR1 variants were conducted to study the impact of the identified mutations. Our findings indicated that the splicing mutation dramatically affected premRNA processing, causing exon 10 and 6 nucleotides in the 3′ end of exon 9 to be completely skipped. Two variants (p.Gly687Arg and p.Ala608Asp) markedly impaired tyrosine kinase activity, while the other variants had limited impact on the mitogen-activated protein kinase (MAPK) signaling pathway. However, the functional impairment of the mutant receptors was not always consistent with the phenotypes, indicating that FGFR1 mutations might cause IHH in conjunction with other mutant genes. In this study, we expanded the knowledge on the mutation spectrum of FGFR1 in IHH patients and explored the genotype-phenotype relationship.     

Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan

Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan, with an incidence of approximately one homozygote in 1000, but is very rare in other countries. Genetic analyses of Japanese C9 deficiency have shown that a C-to-T transition leading to TGA stop codon for Arg95 in exon 4 of the C9 gene (Arg95Stop) is common in Japanese C9 deficiency. To determine the prevalence of heterozygous carriers of the Arg95Stop mutation in a Japanese population, we collected DNA samples from 300 individuals in two of the four main islands of Japan. Heterozygote detection was performed with an allele-specific polymerase chain reaction (PCR) system designed to detect exclusively only one of the normal and mutant alleles, followed by confirmation with PCR/single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Twenty individuals were heterozygous for the Arg95Stop mutation. None was homozygous. The prevalence of carriers of the Arg95Stop mutation was 6.7% (20/300). An estimated frequency (0.12%) of complete C9 deficiency due to homozygous Arg95Stop mutation was consistent with frequencies determined by serological studies. Received: September 22, 1998 / Accepted: November 7, 1998     

Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert's syndrome

Crigler-Najjar syndrome type I is a severe form of hereditary unconjugated hyperbilirubinemia and is caused by homozygous or compound heterozygous mutations of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). We analyzed the bilirubin UDP-glucuronosyltransferase gene in a female Chinese patient with Crigler-Najjar syndrome type I. Relatives of the patient were also analyzed. The patient was homozygous for a nonsense mutation of R341X. The patient's father, sister and brother, all diagnosed with Gilbert's syndrome, were compound heterozygotes of R341X, P229Q, and an insertion mutation of the TATA box [A(TA)7TAA]. Heterozygotes of nonsense mutations (Q331X and C280X) in our previous study had either Crigler-Najjar syndrome type II or Gilbert's syndrome, but heterozygotes of R341X (mother and grandmothers) were normal. An in vitro expression study of homozygous and heterozygous models of R341X showed 0 and 58%, respectively, of normal enzyme activity. Therefore, the present results indicate that carriers of the nonsense mutation could be normal for plasma bilirubin concentration, Gilbert's syndrome and Crigler-Najjar syndrome type II. The results also suggest the importance of the accumulation of prevalent or polymorphic mutation in the etiology of Gilbert's syndrome and Crigler-Najjar syndrome type II.     

A Novel DHCR7 Mutation in a Smith-Lemli-Opitz Syndrome Infant Presenting with Neonatal Cholestasis

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome caused by a defect in cholesterol biosynthesis. The incidence is very low in Asians and only one case has been reported in Korea thus far. Recently, we found an infant with neonatal cholestasis. He had microcephaly, ambiguous genitalia, cleft palate, syndactyly of toes, patent ductus arteriosus and hypertrophic pyloric stenosis. The serum cholesterol was decreased and serum 7-dehydrocholesterol was markedly elevated. Genetic analysis of the DHCR7 gene identified a novel missense mutation (Pro227Ser) as well as a known mutation (Gly303Arg) previously identified in a Japanese patient with SLOS. Although rare in Korea, SLOS should be considered in the differential diagnosis of neonatal cholestasis, especially in patients with multiple congenital anomalies and low serum cholesterol levels.     

The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia

A directly reacting fraction of bilirubin that is probably covalently bound to albumin (albumin-bound bilirubin) has recently been described. To determine its clinical importance we used a new high-performance liquid-chromatography technique to measure it in the serum of 200 patients with hyperbilirubinemia from various causes. Albumin-bound bilirubin was an important fraction (8 to 90 per cent) of total bilirubin in patients with hepatocellular and cholestatic jaundice as well as in patients with the Dubin-Johnson syndrome. It was not detected in normal volunteers, neonates with physiologic jaundice, or patients with Gilbert's disease or hemolysis. Thus, albumin-bound bilirubin appears in serum when hepatic excretion of conjugated bilirubin is impaired. It becomes a larger component of serum bilirubin as jaundice subsides, delaying resolution of this disorder and causing bilirubin to persist in plasma after it has disappeared from the urine.     

Frequencies of UDP-glucuronosyltransferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil

A polymorphism in the promoter region of the UDP-glucuronosyltransferase 1 (UGT1A) gene is associated with Gilbert syndrome (GS), a benign form of mild unconjugated hyperbilirubinemia. We genotyped 157 individuals from Brazil, comprising 71 Caucasians, 54 African-derived subjects, and 32 Parakan? Indians. Frequencies of the alelle (TA)(7) associated with GS found in this study were 0.324, 0.407, and 0.328, respectively. The genotype frequencies differed significantly between Caucasians and African-derived individuals. The high frequencies of (TA)(7) polymorphism among the three groups confirm previous data that this polymorphism is very ancient and appears to be distributed throughout the world.     

Frequencies of UDP‐glucuronosyltransferase 1 (UGT1A1) gene promoter polymorphisms among distinct ethnic groups from Brazil

A polymorphism in the promoter region of the UDP‐glucuronosyltransferase 1 (UGT1A) gene is associated with Gilbert syndrome (GS), a benign form of mild unconjugated hyperbilirubinemia. We genotyped 157 individuals from Brazil, comprising 71 Caucasians, 54 African‐derived subjects, and 32 Parakanã Indians. Frequencies of the alelle (TA)₇ associated with GS found in this study were 0.324, 0.407, and 0.328, respectively. The genotype frequencies differed significantly between Caucasians and African‐derived individuals. The high frequencies of (TA)₇ polymorphism among the three groups confirm previous data that this polymorphism is very ancient and appears to be distributed throughout the world. © 2002 Wiley‐Liss, Inc.     

Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder which is characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. The skeletal muscle calcium channel -subunit gene CACNA1S is a major disease-causing gene for HypoPP, however, only three specific HypoPP-causing mutations, Arg528His, Arg1,239His and Arg1,239Gly, have been identified in CACNA1S to date. In this study, we studied a four-generation Chinese family with HypoPP with 43 living members and 19 affected individuals. Linkage analysis showed that the causative mutation in the family is linked to the CACNA1S gene with a LOD score of 6.7. DNA sequence analysis revealed a heterozygous C to G transition at nucleotide 1,582, resulting in a novel 1,582CG (Arg528Gly) mutation. The Arg528Gly mutation co-segregated with all affected individuals in the family, and was not present in 200 matched normal controls. The penetrance of the Arg528Gly mutation was complete in male mutation carriers, however, a reduced penetrance of 83% (10/12) was observed in female carriers. No differences were detected for age-at-onset and severity of the disease (frequency of symptomatic attacks per year) between male and female patients. Oral intake of KCl is effective in blocking the symptomatic attacks. This study identifies a novel Arg528Gly mutation in the CACNA1S gene that causes HypoPP in a Chinese family, expands the spectrum of mutations causing HypoPP, and demonstrates a gender difference in the penetrance of the disease.Qiufen Wang and Mugen Liu contributed equally to this work     

Glucose-6-phosphate dehydrogenase deficiency in Chinese

In a Chinese population 1,000 full-term male neonates and a further 117 jaundiced neonates of both sexes were studied in an investigation of the frequency of deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G6PD). This enzyme was found to be deficient in 3.6% of male neonates. Correlation of the results with the birthplace of the 602 mothers who were known to come from Kwangtung province showed no significant differences in the frequency of the deficiency between certain parts of the province.The deficiency of G6PD in hemizygous males is profound but it is not associated with erythrocyte acid monophosphoesterase deficiency in Chinese in Hong Kong. The G6PD deficiency accounts for 15.4% of all the 117 cases of neonatal jaundice. The relative importance of G6PD deficiency as a cause of neonatal jaundice does not differ materially in male and female mutants. Neonatal jaundice can occur in all genotypes of G6PD mutation in Chinese.     

Analysis of beta2-adrenergic receptor gene (beta2AR) Arg16Gly polymorphism in patients with endogenous hypertriglyceridemia in Chinese population]

OBJECTIVE: To investigate the Arg16Gly polymorphism of beta2-adrenergic receptor (beta2AR) gene and its association with endogenous hypertriglyceridemia (HTG) in Chinese population. METHODS: Three hundred and forty one subjects including 100 HTG patients and 241 healthy controls from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). RESULTS: The frequencies of Gly allele at the Arg16Gly locus in combined group was 0.446, and were 0.427 and 0.490 in normal and HTG group, respectively. No significant difference was found in both allele and genotype frequencies between normal control and HTG group. The frequency of Gly allele at the Arg16Gly locus in beta2-adrenergic receptor gene in the population (0.446) was similar to that of Japanese (0.505), higher than that of American white(0.248), and lower than that of Polish population (0.633). In normal controls, subjects with genotype Arg/Arg had a higher concentration of serum TG and apoB100, and lower apoAII levels, when compared with those with genotypes Arg/Gly or Gly/Gly, respectively (vs. Arg/Gly for TG, vs. Gly/Gly for apoB100 and apoAII, respectively, P<0.05). In HTG group, subjects with genotype Arg/Arg had higher serum TC and low-density lipoprotein cholesterol levels when compared with those with Gly/Gly genotype (5.36+/-0.74 mmol/L vs. 4.77+/-1.07 mmol/L,P<0.05;3.03+/-0.70 mmol/L vs. 2.38+/-1.10 mmol/L,P<0.05). CONCLUSION: These results suggest that the Arg16Gly polymorphism in beta2-adrenergic receptor gene are not only associated with serum TG,apoB100 and apoAII levels in the healthy Chinese subjects in Chengdu area, but also with serum TC and low-density lipoprotein cholesterol levels in subjects with endogenous hypertriglyceridemia. The Arg16Gly polymorphism in beta2-adrenergic receptor gene may be associated with TG and/or cholesterol metabolism in Chinese Han population.     

Platelet glycoprotein (GP) V polymorphisms in Japanese

The glycoprotein (GP) V is a subunit of a platelet receptor for von Willebrand factor, the GPIb/IX/V complex. Recently, polymorphisms in the GPV gene, four involving amino acid changes and five silent, were identified. We developed an allele-specific restriction method to determine the gene frequencies of the non-synonymous substitutions in Japanese and Caucasians. The gene frequencies for 341Gly/Arg polymorphism were 0.94 for 341Gly and 0.06 for 341Arg, and 0.95 for 341Gly and 0.05 for 341Arg, in Japanese and Caucasians, respectively. We could not find rare variants for 114Asp/Tyr, 273Met/Ile or 397Leu/Arg. Flow cytometric analysis showed that the 341Arg variant is expressed normally on the platelet membranes, suggesting the possibility of the involvement of the 341Gly/Arg polymorphism as a platelet alloantigen.