No abstract

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes Steinthorsdottir, V.; Thorleifsson, G.; Reynisdottir, I.; Benediktsson, R.; Jonsdottir, T.; Walters, G.B.; Styrkarsdottir, U.; Gretarsdottir, S.; Emilsson, V.; Ghosh, S.

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

A known history of diabetes and ambient hyperglycaemia were independent predictors for death and morbidity in SARS patients. Metabolic control may improve the prognosis of SARS patients.

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early β cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young-onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular–renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens.

Overweight and obesity have become a major public health problem in both developing and developed countries as they are causally related to a wide spectrum of chronic diseases including type II diabetes, cardiovascular diseases and cancer. However, uncertainty regarding the most appropriate means by which to define excess body weight remains. Traditionally, body mass index (BMI) has been the most widely used method by which to determine the prevalence of overweight in, and across, populations as well as an individual's level of risk. However, in recent years, measures of central obesity, principally waist circumference and the waist:hip ratio and to a lesser extent the waist:height ratio, which more accurately describe the distribution of body fat compared with BMI, have been suggested to be more closely associated with subsequent morbidity and mortality. There is also uncertainty about how these measures perform across diverse ethnic groups; earlier, most of the evidence regarding the relationships between excess weight and risk has been derived chiefly from Caucasian populations, and hence, it remains unclear whether the relationships are consistent in non-Caucasian populations. The purpose of this review, therefore, is to provide an overview of the current evidence-base focusing predominantly on three main questions: (1) Which, if any, of the commonly used anthropometric measures to define excess weight is more strongly associated with cardiovascular risk? (2) Which of the anthropometric measures is a better discriminator of risk? and (3) Are there any notable differences in the strength and nature of these associations across diverse ethnic groups?

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.