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Abstract Background Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. Methods This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. Results Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P

Abstract Background Impaired fasting glucose (IFG) is a prevalent and potentially reversible intermediate stage leading to type 2 diabetes that increases risk for cardiometabolic complications. The identification of clinical and molecular factors associated with the reversal, or regression, from IFG to a normoglycemia state would enable more efficient cardiovascular risk reduction strategies. The aim of this study was to identify clinical and biological predictors of regression to normoglycemia in a non-European population characterized by high rates of type 2 diabetes. Methods We conducted a prospective, population-based study among 9637 Mexican individuals using clinical features and plasma metabolites. Among them, 491 subjects were classified as IFG, defined as fasting glucose between 100 and 125 mg/dL at baseline. Regression to normoglycemia was defined by fasting glucose less than 100 mg/dL in the follow-up visit. Plasma metabolites were profiled by Nuclear Magnetic Resonance. Multivariable cox regression models were used to examine the associations of clinical and metabolomic factors with regression to normoglycemia. We assessed the predictive capability of models that included clinical factors alone and models that included clinical factors and prioritized metabolites. Results During a median follow-up period of 2.5 years, 22.6% of participants (n = 111) regressed to normoglycemia, and 29.5% progressed to type 2 diabetes (n = 145). The multivariate adjusted relative risk of regression to normoglycemia was 1.10 (95% confidence interval [CI] 1.25 to 1.32) per 10 years of age increase, 0.94 (95% CI 0.91–0.98) per 1 SD increase in BMI, and 0.91 (95% CI 0.88–0.95) per 1 SD increase in fasting glucose. A model including information from age, fasting glucose, and BMI showed a good prediction of regression to normoglycemia (AUC = 0.73 (95% CI 0.66–0.78). The improvement after adding information from prioritized metabolites (TG in large HDL, albumin, and citrate) was non-significant (AUC = 0.74 (95% CI 0.68–0.80), p value = 0.485). Conclusion In individuals with IFG, information from three clinical variables easily obtained in the clinical setting showed a good prediction of regression to normoglycemia beyond metabolomic features. Our findings can serve to inform and design future cardiovascular prevention strategies.

Abstract Background Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. Results We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r 2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r 2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r 2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r 2 = 0.972. Conclusions Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals.

Abstract Background FSHR SNPs may influence the ovarian sensitivity to endogenous and exogenous FSH stimulation. Given the paucity of data on the FSHR c.919A > G, c.2039A > G and − 29G > A SNPs in Hispanic population, we here analyzed their frequency distribution in Mexican mestizo women. Methods Samples from 224 Mexican mestizo women enrolled in an IVF program as well as a genotype database from 8182 Mexican mestizo subjects, were analyzed for FSHR SNPs at positions c.919, c.2039 and − 29G > A. Association between the genetic variants and reproductive outcomes was assessed. Results The c.919 and c.2039 SNPs were in strong linkage disequilibrium and their corresponding genotype frequencies in the IVF group were: AA 46.8%, AG 44.2%, and GG 8.9%, and AA 41.9%, AG 48.2% and GG 9.8%, respectively. For the -29G > A SNP, genotype frequencies were 27% (GG), 50% (GA) and 23% (AA). In normal oocyte donors with the c.2039 GG genotype, the number of oocytes recovered after ovarian stimulation (COS) were significantly (p A SNP. Analysis of the large scale database revealed that both allelic and genotype frequencies for the three SNPs were very similar to those detected in the IVF cohort (p ≥ 0.38) and that female carriers of the c.2039 G allele tended to present lower number of pregnancies than women bearing the AA genotype; this trend was stronger when women with more Native American ancestry was separately analyzed (OR = 2.0, C.I. 95% 1.03–3.90, p = 0.04). There were no differences or trends in the number of pregnancies among the different genotypes of the -29G > A SNP. Conclusions The frequency of the GG/GG combination genotype for the c.919 and c.2039 SNPs in Mexican hispanics is among the lowest reported. The GG genotype is associated with decreased number of oocytes recovered in response to COS as well as to lower pregnancy rates in Hispanic women from the general population. The absence of any effect of the -29AA genotype on the response to COS, indicates that there is no need to perform this particular genotype testing in Hispanic women with the purpose of providing an individually-tailored COS protocol.