Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects: A Strobe Compliant Article.

Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy.

The MTRR 66A>G polymorphism and maternal risk of birth of a child with Down syndrome in Caucasian women: a case-control study and a meta-analysis.

We performed a large case-control study and a meta-analysis of the literature to address the role of the methionine synthase reductase (MTRR) c.66A>G polymorphism as a maternal risk factor for the birth of a child with Down Syndrome (DS) among Caucasian women. A total of 253 mothers of a DS child (MDS) and 298 control mothers of Italian origin were included in the case-control study.

"Postural first" principle when balance is challenged in elderly people.

Human cognitive processing limits can lead to difficulties in performing two tasks simultaneously. This study aimed to evaluate the effect of cognitive load on both simple and complex postural tasks. Postural control was evaluated in 128 noninstitutionalized elderly people (mean age = 73.

Biological determinants of postural disorders in elderly women.

Postural control impairments and dizziness, which are major health problems with high secondary morbidity and mortality, increase with aging. Elevated homocysteine (Hcy) level is an age-related metabolic disorder, known to be involved in cardiovascular, neurological, and multisensory dysfunctions. Elevated Hcy level might be involved in sensory balance control systems impairment and dizziness occurrence.

Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population.

Objective: The ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models.

Prevalence of dementia in mountainous village of Sicily.

The progressive and rapid aging of population is the demographic characteristic in the Western countries. This rapid process of aging is causing an increasing burden on the social and health-care services. In this context, the precise knowledge of the environmental, socio-economical and clinical characteristics of the elderly population is mandatory to find the correct strategies to achieve the successful aging.

Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily.

Background: Association of thyroid dysfunction with plasma homocysteine levels and vitamin B(12) has previously been reported. We evaluated these associations in the elderly in San Teodoro, a mountainous village of Sicily.

Methods: Subjects (n=279) aged 60-85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests.

Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily.

Background: Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine.

Methods: Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests.

Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2).

Background: A 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B(12).

Objective: To evaluate the worldwide prevalence of this variant and its association with homocysteine plasma level.

Methods: The study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and in 251 Afro-Africans participants with severe malaria.

Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily.

Association between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T ), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin ( TCN2 ) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily.

Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations.

Background: Methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism is heterogeneously distributed worldwide, with the highest and lowest frequencies of the T allele in Mexico and Africa, respectively, and a south-to-north gradient in Europe. Distribution of MTHFR 1298A-->C is less well known. It has been hypothesized that 677T frequency could result in part from gene-nutrient interactions.

Allele epsilon 4 of APOE is a stronger predictor of Alzheimer risk in Sicily than in continental South Italy.

The genotype of apolipoprotein E was examined in 173 sporadic Alzheimer's disease (AD) patients, 132 with late onset (LOAD) and 41 with early onset (EOAD), and in 174 healthy matched controls from Sicily. Despite a low frequency of the epsilon 4 allele (6.3%, 95% CI: 4.

Homocysteine and methylenetetrahydrofolate reductase polymorphism in Alzheimer's disease.

Homocysteine metabolism is influenced by genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR 677 C-->T and 1298 A-->C) and transcobalamin genes (TCN1 776 C-->G ). We evaluated the association of homocysteine with Alzheimer's disease (AD) and the influence of related polymorphisms and APOE, in 180 cases and 181 controls from southern Italy. Homocysteine (upper tercile) was associated with AD risk, with an odds ratio of 2.

Genetic determinants of folate and vitamin B12 metabolism: a common pathway in neural tube defect and Down syndrome?

One-carbon metabolism is under the influence of folate, vitamin B12 and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C --> T and 1298 A --> C), of methionine synthase (MTR 2756 C --> G), methionine synthase reductase (MTRR 66 A --> G) and transcobalamin (TCN 776 C --> G). The pathogenesis of neural tube defect (NTD) may be related to this metabolism. The influence of the MTHFR 677 C --> T polymorphism reported in The Netherlands and Ireland can be questioned in southern Italy, France and Great Britain.

Methionine synthase (MTR) 2756 (A --> G) polymorphism, double heterozygosity methionine synthase 2756 AG/methionine synthase reductase (MTRR) 66 AG, and elevated homocysteinemia are three risk factors for having a child with Down syndrome.

Contradictory findings have been recently published on the evaluation of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C-->T) and methionine synthase reductase (MTRR 66 A-->G) as risk factors for having a child with Down syndrome (DS); however, the influence of polymorphisms of methionine synthase (MTR 2756 A-->G) and of MTHFR 1298 A-->C has never been evaluated. In this study, the risk of being a DS case or having a DS child (case mother) was studied by multiple logistic regression analysis of the independent and combined genotypes and of plasma homocysteine, folates, and vitamin B12 in 92 DS cases and 140 control subjects as well as in 63 case mothers and 72 age-matched control mothers from Sicily. (The MTHFR 677 T allele frequency was not different in DS cases and case mothers, compared to the respective control groups).