Dr. Hsien-Hsien Lei

The Coronavirus disease 2019 (COVID-19) pandemic has had an immense impact infecting 10 million individuals and claiming 500,000 lives globally as of 1 July 2020 (1). The rapid spread was largely enabled by the onset of the outbreak in Wuhan city just prior to the Lunar New Year season, a peak period in travel to and from China (2). Fortunately, many regions have controlled initial outbreaks and shared their experiences. These have been recently summarized by the World Health Organization… Show more

The Coronavirus disease 2019 (COVID-19) pandemic has had an immense impact infecting 10 million individuals and claiming 500,000 lives globally as of 1 July 2020 (1). The rapid spread was largely enabled by the onset of the outbreak in Wuhan city just prior to the Lunar New Year season, a peak period in travel to and from China (2). Fortunately, many regions have controlled initial outbreaks and shared their experiences. These have been recently summarized by the World Health Organization (WHO), highlighting the importance of developing targeted responses and enhancing communication to address the pandemic’s impact (3, 4).

Notably, emotionally driven sharing of misinformation has featured prominently in this crisis, fueling both confusion and irrational anxiety among the public (5, 6). Termed an “infodemic”, this has far-reaching consequences on population health with a direct impact on overloaded health systems and an indirect impact on mental health, resulting in paranoia and behavioral responses like stock-piling due to disproportionate fear (7). The impact of misinformation in the media on public emotion and fear has been illustrated with the Middle-East Respiratory Syndrome (MERS), whereby it led to a surge in fear and sustained economic consequences (8). Show less

These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than… Show more

These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than symptomatic or clinical BPH. Show less

To address the role of PPARγ2 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 PPARγ2… Show more

To address the role of PPARγ2 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 PPARγ2, 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 PPARγ2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. 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 PPARγ2 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 PPARγ2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations. Show less

he peroxisome proliferator—activated receptor gamma 2 (PPARγ2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARγ2 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)… Show more

he peroxisome proliferator—activated receptor gamma 2 (PPARγ2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARγ2 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 PPARγ 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. Show less

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.

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… Show more

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. Show less

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… Show more

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. Show less

A population-based case-control study was conducted in WashingtonCounty, Maryland (United States) to explore the association between incidentbladder cancer and exposure to drinking water from chlorinated surfacesources. Cancer cases were White residents, enumerated in a 1975 countycensus 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)… Show more

A population-based case-control study was conducted in WashingtonCounty, Maryland (United States) to explore the association between incidentbladder cancer and exposure to drinking water from chlorinated surfacesources. Cancer cases were White residents, enumerated in a 1975 countycensus 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). Householdsreceiving municipal water, which generally derived from chlorinated surfacewaters, were treated as having ‘high exposure‘ and all others, as ‘lowexposure.’ Duration of exposure to type of drinking water was based on lengthof residence in the census household prior to 1975. Odds ratios (OR) werecalculated using logistic regression methods, adjusting for age, gender,tobacco use, and urbanicity. Bladder cancer risk was associated weakly in thegeneral population with duration o f exposure to municipal water. Theassociation was limited to those who had smoked cigarettes. In ever-smokerscompared with never-smokers with low exposure, the adjusted ORs for bladdercancer 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' exposureduration. The ORs in smokers were not diminished after adjusting for smokinghistory and intensity. Show less

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… Show more

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. Show less