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H H Lei

Publications and source records attributed to H H Lei.

9 recordsLinked to original sources
PubMed2001

Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our results suggest that within families siblings with the A variant in the PPARgamma2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations.

Adult↗
PubMed2000

Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Vitamin D and its receptor have been suggested to play a role in the pathogenesis of type 1 diabetes mellitus. We have therefore studied the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes, and rates of glutamic acid decarboxylase (GAD65) autoantibody and islet cell autoantibody (ICA512) positivity. SUBJECTS: AND MEASUREMENTS One hundred and fifty-seven type 1 diabetic patients and 248 unrelated normal controls were recruited for this study. Genomic DNA was extracted from peripheral blood leucocytes. All type 1 diabetic patients and controls were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), for three restriction sites in the VDR gene, BsmI, ApaI and TaqI. The chi2 test was used to compare the frequency of the VDR gene polymorphisms in patients and normal controls. The association of VDR gene polymorphisms in type 1 diabetes with the presence of GAD65 and ICA512 autoantibodies were also examined using the chi2 test. RESULTS: The allele frequency of the BsmI and ApaI polymorphisms, but not TaqI polymorphism, differed between patients and controls (BsmI P = 0.015; ApaI P = 0.018; TaqI P = 0.266). However, after correction for the three different polymorphisms tested, only the BsmI was significant (pc = 0.045). CONCLUSIONS: Vitamin D receptor gene polymorphisms were associated with type 1 diabetes in a Taiwanese population. However, functional studies are needed to establish the role of the vitamin D receptor in the pathogenesis of type 1 diabetes mellitus.

Adolescent↗
PubMed2000

Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese.

The peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARgamma2 gene variants with type 2 diabetes mellitus, the body mass index (BMI), and other diabetes-related phenotypes was examined in the Taiwanese population. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele frequencies were compared between 280 subjects with type 2 diabetes mellitus and 310 subjects without diabetes using the chi-square test. Continuous phenotype analysis was performed by multiple logistic regression adjusting for age and BMI where appropriate. There was no significant association between the Pro12Ala gene variant and type 2 diabetes; the frequency of the Ala12 allele was 0.03 in type 2 diabetics and 0.04 in nondiabetics (P = .40). The Gln115 allele was not detected in any of the cases or controls. In multiple linear regression analysis of all cases and controls combined adjusted for age, sex, and diabetic status, carriers of the Ala12 allele had a mean BMI of 25.9+/-0.5 kg/m2 (mean +/- SE), compared with 24.2+/-0.1 kg/m2 in Pro12 homozygotes (P < .001). In addition, carriers of the Ala12 allele have a 2.9 times (95% confidence interval [CI], 1.5 to 5.5) higher odds of having a BMI of at least 25 kg/m2. These results suggest that in the Taiwanese, the Pro12Ala PPARgamma2 gene variant may contribute to fat accumulation and a higher BMI independent of type 2 diabetes. These results need to be confirmed in future studies, as a linkage disequilibrium of this variant with other mutations cannot be ruled out.

Adult↗
PubMed1999

Variants of the insulin receptor substrate-1 and fatty acid binding protein 2 genes and the risk of type 2 diabetes, obesity, and hyperinsulinemia in African-Americans: the Atherosclerosis Risk in Communities Study.

We conducted a community-based case-control study of African-American men and women in the Atherosclerosis Risk in Communities Study. The allele frequencies of the Gly972Arg variant of the insulin receptor substrate-1 (IRS-1) gene and the Ala54Thr variant of the fatty acid binding protein 2 (FABP2) gene were compared in 992 normal control subjects and three patient groups: 1) 321 type 2 diabetic individuals, 2) 260 severely obese individuals, and 3) 258 markedly hyperinsulinemic individuals without diabetes. Allele frequencies of Gly972Arg IRS-1 and Ala54Thr FABP2 were 0.07 and 0.22, respectively; there were no differences in allele or genotype frequencies between patients and control subjects for either gene variant. In weighted linear regression of all patients and control subjects, the presence of the IRS-1 gene variant was associated with a 0.85 (0.42) kg/m2 higher BMI (P = 0.04). In addition, individuals with at least one IRS-1 Arg972 allele and two FABP2 Thr54 alleles had a BMI of 33.3 (7.9) kg/m2, compared with 30.0 (6.3) kg/m2 for those with neither allele (P = 0.05). These results suggest that in African-Americans, these variants in the IRS-1 and FABP2 genes are not associated with the risk of type 2 diabetes, severe obesity, or marked hyperinsulinemia, but that their independent and joint effects may be associated with small increases in BMI.

Arteriosclerosis↗
PubMed1998

Familial aggregation of renal disease in a population-based case-control study.

Family history of renal disease has been associated with an increased risk of end-stage renal disease (ESRD). It is uncertain whether this risk is mediated by familial aggregation of risk factors for ESRD, such as diabetes and hypertension. The association of ESRD with familial aggregation of renal disease was examined in a large, population-based case-control study conducted in Maryland, Virginia, West Virginia, and Washington, DC. The number of first-degree relatives who were affected with any type of renal disease was compared between 689 newly treated ESRD patients registered in the Medicare ESRD program (92% of all eligible incident cases presenting between January and July of 1991) and 361 control subjects without ESRD who were selected by random-digit dialing (90% response rate). Patients and control subjects were frequency matched by age; patients with ESRD caused by polycystic kidney disease and other known hereditary kidney diseases were excluded. Analysis was conducted using multiple logistic regression. After controlling for the proband's age, gender, race, family size, socioeconomic status, and personal and family histories of diabetes and hypertension, having one first-degree relative with renal disease increased the odds of ESRD by 1.3 (95% confidence interval, 0.7 to 2.6) and having two or more affected first-degree relatives increased the odds of ESRD by 10.4 (95% confidence interval, 2.7 to 40.2). These data support familial aggregation of renal disease in excess of that predicted by clustering of diabetes and hypertension within families, suggesting that either genetic susceptibility or environmental exposures shared within families increase the risk of developing ESRD. This risk is also much higher when two or more first-degree relatives have renal disease. Unraveling the molecular basis of this increase in risk may provide new avenues for treatment and prevention of ESRD.

Adult↗
PubMed1997

A comprehensive analysis of complex traits in problem 2A.

We used descriptive analysis to investigate the relationship between affection status and five quantitative traits (Q1-Q5) in Problem 2A and results suggested the five quantitative traits fall into two groups. The first group comprised three strongly correlated traits, Q1-Q3, which underlie affection status, and the second group comprised Q4 and Q5, which are not directly related to affection status. Segregation and linkage analyses of traits Q1-Q3 and affection status from the first replicate detected one of the major loci for Q1 (MG1) linked to marker 14 on chromosome 5 (D5G14). Because our segregation analysis failed to show evidence of a major locus effect on Q2, and we overlooked the interaction between MG3 and sex, we did not detect either MG2 or MG3. Using Haseman-Elston sib-pair analysis [Haseman and Elston, 1972], we also examined the statistical power of Q1 and type I error rate (using the environmental factor as an index), for the remaining 199 replicates in the context of a genome screen.

Chromosome Mapping↗
PubMed1997

Bladder cancer and drinking water: a population-based case-control study in Washington County, Maryland (United States).

A population-based case-control study was conducted in Washington County, Maryland (United States) to explore the association between incident bladder cancer and exposure to drinking water from chlorinated surface sources. Cancer cases were White residents, enumerated in a 1975 county census and reported to the Washington County Cancer Registry (n = 294) between 1975 and 1992. White controls, frequency matched by age (+/- 5 years) and gender, were selected randomly from the census (n = 2,326). Households receiving municipal water, which generally derived from chlorinated surface waters, were treated as having 'high exposure' and all others, as 'low exposure.' Duration of exposure to type of drinking water was based on length of residence in the census household prior to 1975. Odds ratios (OR) were calculated using logistic regression methods, adjusting for age, gender, tobacco use, and urbanicity. Bladder cancer risk was associated weakly in the general population with duration of exposure to municipal water. The association was limited to those who had smoked cigarettes. In ever-smokers compared with never-smokers with low exposure, the adjusted ORs for bladder cancer risk with increasing exposure were 1.3, 1.4, 1.4, 1.7, 2.2, 2.8, respectively, for 0, 1-10, 11-20, 21-30, 31-40, > 40 years' exposure duration. The ORs in smokers were not diminished after adjusting for smoking history and intensity.

Adult↗
PubMed1995

Transfection of Plasmodium falciparum within human red blood cells.

Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT-encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparum hsp86, hrp3, and hrp2 genes. These flanking sequences were required for expression as their excision abolished CAT activity in transfected parasites. Transfection signals from native CAT-encoding DNA compared well with those from a synthetic DNA sequence adapted to the P. falciparum major codon bias, demonstrating effective expression of the bacterial sequence despite its use of rare P. falciparum codons. Transfected ring-stage parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts. The transfection of erythrocyte-stage P. falciparum parasites advances our ability to pursue genetic analysis of this major pathogen.

Amino Acid Sequence↗