Body mass index and waist circumference of HIV-infected youth in a Miami cohort: comparison to local and national cohorts.

OBJECTIVES: Human immunodeficiency virus (HIV)-infected youth are healthier because of effective antiretroviral therapies. We compared anthropometric measurements and prevalence of overweight and obesity between perinatally HIV-infected youth, a local HIV-uninfected comparison group, and 2007 to 2010 National Health and Nutrition Examination Survey (NHANES) data. In addition, we compared only African American HIV-infected youth with NHANES African Americans. METHODS: Height, weight, body mass index (BMI), and waist circumference (WC) of HIV-infected youth, aged 10 to 19 years, were compared among groups. BMI percentiles were categorized as underweight (<5%), normal (5% to <85%), overweight (85% to <95%), and obese (≥ 95%). Clinical correlates were modeled as predictors of BMI and WC. RESULTS: A total of 134 HIV-infected (including 103 African Americans) (mean age 16.5 years), 75 HIV-uninfected (mean age 14.2 years), and 3216 NHANES (including 771 NHANES African Americans) (mean age 15.0 years) youth were included in the analysis. Height and weight z scores of HIV-infected youth were lower than those of HIV-uninfected and NHANES (P ≤ 0.056) youth. BMI, WC, and BMI category were not statistically different between groups. In the HIV-infected African American group, BMI z score was lower (0.49 vs 0.76, P = 0.04) compared with NHANES African Americans. There were no significant predictors of BMI or WC for the HIV-infected group. CONCLUSIONS: HIV-infected children have similar BMIs and WCs as uninfected children both locally and nationally and show similar high rates of obesity and overweight. When compared with a more racially similar African American national sample, HIV-infected children have a lower BMI, suggesting that there may be persistent anthropometric differences in HIV.

Discerning the ancestry of European Americans in genetic association studies.

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD.

BACKGROUND: Preclinical and genetic studies have implicated the 5HT1B receptor gene (HTR1B) in attention-deficit/hyperactivity disorder (ADHD). Association with a single nucleotide polymorphism (SNP; G861C) has been observed, but more extensive linkage disequilibrium analyses have not been reported. METHODS: To examine haplotype structure, we genotyped 21 SNPs in and around the gene in 12 multigenerational CEPH pedigrees. We identified a haplotype block encompassing HTR1B and performed haplotype and single-marker association analyses for the eight SNPs within or flanking this block in 229 families of ADHD probands. In light of previous studies suggesting distinct genetic influences on ADHD subtypes, we also examined association with the inattentive and combined subtypes. RESULTS: We observed nonsignificant overtransmission of the G861 allele to ADHD offspring (one-tailed p = .07). Single-marker and haplotype tests of a haplotype block encompassing HTR1B revealed no other associations with ADHD. However, this haplotype block was associated with the inattentive subtype (global p < .01). Additionally, three SNPs in this block were nominally (p < .05) associated with the inattentive subtype, although these did not remain significant after correction for multiple testing. As reported in previous studies, we found paternal overtransmission of the G861 allele to offspring with ADHD; this appeared to be largely attributable to inattentive cases. CONCLUSIONS: These analyses suggest that variation in the HTR1B gene may primarily affect the inattentive subtype of ADHD.

Investigation of parent-of-origin effects in ADHD candidate genes.

Attention deficit hyperactivity disorder (ADHD) is a common early-onset childhood disorder with a strong genetic component. Results from previous studies have suggested that there may be a parent-of-origin effect for ADHD candidate genes. In particular, a recent investigation identified a pattern of paternal over-transmission of risk alleles for nine ADHD candidate genes. We examined this phenomenon in a sample of 291 trios for five genes previously associated with ADHD (HTR1B, SNAP-25, DRD5, DAT1, and BDNF). Using a dense map of markers and two analytic methods in this relatively large family-based sample, we do not find any evidence for significant paternal over-transmission of risk alleles in these candidate loci. Thus, we conclude that a substantial parent-of-origin effect is unlikely for these leading ADHD candidate genes.

Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility.

Estrogen production and metabolism play critical roles in the development and pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. We evaluated the association between the CYP1B1 Leu432Val and CYP1B1 Asn453Ser polymorphisms and the COMT Val158Met polymorphism and invasive endometrial cancer risk in a case-control study nested within the Nurses' Health Study (n = 222 cases, 666 controls). We also evaluated whether body mass index (BMI), postmenopausal hormone (PMH) use and cigarette smoking modified the associations of the CYP1B1 and COMT genotypes and endometrial cancer risk. Conditional logistic regression was used to calculate the adjusted odds ratios (OR) and 95% confidence intervals (CI) to quantify the risk of endometrial cancer among subjects who had at least one variant allele compared with subjects who were homozygous for the wild-type allele. Carriers of the CYP1B1 Ser allele had a statistically significant decreased risk of endometrial cancer (OR = 0.62; 95% CI, 0.42-0.91); there was no significant association between the CYP1B1 Val allele and endometrial cancer risk (OR = 1.10; 95% CI, 0.75-1.59). Compared with the COMT Val/Val wildtype genotype, the adjusted OR of endometrial cancer for women with the COMT Val/Met or COMT Met/Met genotype was 0.96 (95% CI, 0.65-1.43). We did not observe any effect modification by BMI, PMH use and cigarette smoking for the CYP1B1 and COMT genotypes. Our data suggest, that the CYP1B1 Ser allele may decrease endometrial cancer risk by altering the production of catechol estrogens. However, further studies are warranted to elucidate the role of CYP1B1 in endometrial cancer.