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.

Arsenic toxicity in Hawaii: a case report and review.

As mentioned at the beginning of this article, many questions were raised in our one particular case including the problem of verifying true arsenic toxicity and in determining the source of the exposure. In our case, there was a markedly elevated concentration of arsenic in samples of pubic hair and in the sample of urine. While arsenic toxicity can present with GI symptoms, we felt that in this particular case the association of the abdominal pain with arsenic toxicity was unlikely. For one, the patient's symptoms persisted despite apparent adequate treatment for arsenic toxicity. Also, the usual symptom of chronic arsenic toxicity is peripheral neuropathy (which was not documented in our case) and not abdominal pain. After the exhaustive diagnostic workup, we felt that this patient had irritable bowel syndrome and that the discovery of arsenic toxicity was serendipitous. In regards to the etiology of the toxicity, the patient's occupation involved working in the construction industry for a number of years. He indicated a definite exposure to termite-treated wood throughout that period. Wood for building houses, etc. is commonly pressure-treated with an arsenic-based compound; therefore, this source of occupational exposure appears to be a likely one. Another remotely possible source was the ingestion of contaminated illicit drugs. Cases of the use of illicit drugs laced with various toxic agents such as cyanide and strychnine have been reported. Although our patient required analgesics not commensurate with his symptoms, he categorically denied any use of "street" drugs. The random urine drug screen for such was negative.(ABSTRACT TRUNCATED AT 250 WORDS)