Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.

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Adrenergic receptor polymorphism and obesityrelated phenotypes in hypertensive patients. Obes Res. 2004;12:125-130. Objectives: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The ␤ 3 adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. Research Methods and Procedures: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men, 359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. Results: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p Ͻ 0.001) and had a BMI that was 3.7 kg/m 2 greater (p ϭ 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. Discussion: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.

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Bottlebrush polymers exhibiting unique properties have attracted considerable attention for applications in many research areas. Herein, the first simultaneous synthesis and self‐assembly of bottlebrush block copolymers at room temperature via photoinitiated polymerization‐induced self‐assembly (photo‐PISA) using multifunctional macromolecular chain transfer agents (macro‐CTAs) is reported. Comparing with linear block copolymers, the bottlebrush block copolymers can promote the formation of higher‐order morphologies (e.g., vesicles) when targeting similar degrees of polymerization (DPs). Moreover, a higher polymerization rate is observed in the case of bottlebrush block copolymers. Gel permeation chromatography (GPC) analysis shows that good polymerization control is maintained when synthesizing bottlebrush block copolymers by photo‐PISA. Finally, the obtained bottlebrush block copolymer vesicles are used as seeds for further chain extension and multicompartment nanoparticles with a sponge internal structure are formed. It is expected that this study will not only expand polymer architectures employed in PISA, but also provide a new strategy to synthesize polymer nanoparticles with unique structures.