OBJECTIVEParental diabetes history is a well-known risk factor for type 2 diabetes and considered strong evidence for a genetic basis of type 2 diabetes. Whether this relationship is affected by other known risk factors, specifically obesity, remains unclear, possibly due to a relative paucity of lean diabetic patients.RESEARCH DESIGN AND METHODSThis issue was investigated using data from a high-risk population from Mexico (National Health Survey 2000, n = 27,349), with observations replicated using U.S. citizens of Mexican descent from the National Health and Nutrition Examination Survey 2001–2002 and 2003–2004 (n = 1,568).RESULTSAs expected, positive parental diabetes was a significant risk factor for type 2 diabetes, regardless of age, sex, or adiposity level. However, positive parental diabetes conferred greater risk in leaner individuals than in their overweight peers (P = 0.001). In other words, the effect of BMI on type 2 diabetes risk was smaller in the presence of parental diabetes history.CONCLUSIONSThese findings suggest that parental diabetes is a stronger risk factor for type 2 diabetes in the absence of obesity. Thus, studies in lean diabetic patients could help identify type 2 diabetes susceptibility genes. This study reinforces the concept that parental diabetes and BMI are independent type 2 diabetes risk factors and suggests that glycemic screening may be helpful in assessing type 2 diabetes risk in individuals with parental diabetes history, regardless of their overweight status.
Little research has been undertaken on risk factors for obesity in young people in Latin America, including Mexico, despite the fact that obesity constitutes the number one public health problem in Mexico. Our objective was to investigate the effect of the Peroxisome proliferators-activated receptor (PPAR)_3 gene on BMI measured among adolescents collected from a cohort study originally designed for epidemiological studies. METHODS: Blood samples and anthropometric measurements were collected from 1,210 out of 13,294 public school students of both sexes, aged 11-24 years in Morelos, Mexico. In this study, we genotyped 7 selected SNPs of the PPAR_ transcript variant 3 (including Pro12Ala) in a group of unrelated 717 males and 493 females (age range 11-24), including 3 SNPs located in the 5' untranslated region. These 7 SNPs were selected by the tagging algorithm implemented in the program haploview to scan the whole gene. We tested each of the 7 SNPs individually for association with the body mass index (BMI), and two SNPs (rs2938392 and rs1175542) revealed significant associations with BMI (p-value=0.008 and 0.029, respectively). The SNP rs2938392 is roughly 41.5 Kb from rs1801282 (Pro12Ala in PPAR_2). Furthermore, we examined the association between haplotypes built from 7 SNPs and BMI using a score statistic implemented in the program haplo.stats. While the permutation based global p-value was 0.544, one individual haplotype with a frequency of 0.279 gave a p-value of 0.089 * This work is supported by Glaxo-Smith-Kline Epidemiology † This work is partially supported by University of Bristol Pacific Symposium on Biocomputing 11:467-477(2006) (permutation based). However, when the analyses were conducted in males only, the permutation based global p-value was 0.055 and one individual haplotype with a frequency of 0.28 gave a significant p-value of 0.013.
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