-
1.
Impact of the Association Between PNPLA3 Genetic Variation and Dietary Intake on the Risk of Significant Fibrosis in Patients With NAFLD.
Vilar-Gomez, E, Pirola, CJ, Sookoian, S, Wilson, LA, Belt, P, Liang, T, Liu, W, Chalasani, N
The American journal of gastroenterology. 2021;(5):994-1006
-
-
Free full text
-
Abstract
INTRODUCTION This study explored the relationship between patatin-like phospholipase domain-containing 3 gene (PNPLA3 rs738409), nutrient intake, and liver histology severity in patients with nonalcoholic fatty liver disease (NAFLD). METHODS PNPLA3-rs738409 variant was genotyped in 452 non-Hispanic whites with histologically confirmed NAFLD who completed Food Frequency Questionnaire within 6 months of their liver biopsy. The fibrosis severity on liver histology was the outcome of interest. RESULTS The distribution of PNPLA3 genotypes was CC: 28%, CG: 46%, and GG: 25%. High-carbohydrate (% of energy/d) intake was positively associated (adjusted [Adj] odds ratio [OR]: 1.03, P < 0.01), whereas higher n-3 polyunsaturated fatty acids (n-3 PUFAs) (g/d) (Adj. OR: 0.17, P < 0.01), isoflavones (mg/d) (Adj. OR: 0.74, P = 0.049), methionine (mg/d) (Adj. OR: 0.32, P < 0.01), and choline (mg/d) (Adj. OR: 0.32, P < 0.01) intakes were inversely associated with increased risk of significant fibrosis (stage of fibrosis ≥2). By using an additive model of inheritance, our moderation analysis showed that PNPLA3 rs738409 significantly modulates the relationship between carbohydrate (%), n-3 PUFAs, total isoflavones, methionine, and choline intakes and fibrosis severity in a dose-dependent, genotype manner. These dietary factors tended to have a larger and significant effect on fibrosis severity among rs738409 G-allele carriers. Associations between significant fibrosis and carbohydrates (Adj. OR: 1.04, P = 0.019), n-3 PUFAs (Adj. OR: 0.16, P < 0.01), isoflavones (Adj. OR: 0.65, P = 0.025), methionine (Adj. OR: 0.30, P < 0.01), and total choline (Adj. OR: 0.29, P < 0.01) intakes remained significant only among rs738409 G-allele carriers. DISCUSSION This gene-diet interaction study suggests that PNPLA3 rs738409 G-allele might modulate the effect of specific dietary nutrients on risk of fibrosis in patients with NAFLD.
-
2.
Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study.
Liu, X, Wei, D, Jiang, J, Liu, X, Tu, R, Luo, Z, Wang, Y, Dong, X, Qiao, D, Shen, F, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(4):599-607
Abstract
BACKGROUND AND AIM Multiple studies support a complex relationship between testosterone and type 2 diabetes mellitus (T2DM) and the transformation of testosterone is affected by several reductases. Thus, we aimed to explore the associations of steroid-5α-reductase type 1 (SRD5A1) gene polymorphism with impaired fasting glucose (IFG) and T2DM and the interactive effects of testosterone and genotypes on glycometabolism. METHODS AND RESULTS A case-control study including 2365 participants was performed. Genomic DNA was extracted from the whole blood and genotyped for the SRD5A1 single nucleotide polymorphisms (SNP) rs1691053. Multivariable logistic regression and linear regression were performed to estimate the associations of SRD5A1 rs1691053 alleles and genotypes with glycometabolism. Generalized linear models were used to investigate the modulatory effects of serum testosterone on glycometabolism indexes in males. After multivariable adjustment, the odds ratio (OR) of homozygous CC genotypes in male carriers was 2.62 (95%CI: 1.11-6.18) for IFG. Furthermore, significant associations of SRD5A1 rs1691053 polymorphisms with adverse indices of glycometabolism were observed in males. Interestingly, the opposite associations in females were observed. The interactive associations of SNP and testosterone were found and mutations were more likely to lead unfavorable metabolic phenotypes. CONCLUSION These results showed that SRD5A1 rs1691053 gene polymorphism was independently associated with glycometabolism. The interaction between a genetic polymorphism from SRD5A1 and testosterone involved glycometabolism was identified in males. Although this preliminary data should be replicated with other rigorous researches, it highlighted the importance of the SNP-testosterone interaction over the present of glycometabolism.
-
3.
TIMD4 rs6882076 SNP Is Associated with Decreased Levels of Triglycerides and the Risk of Coronary Heart Disease and Ischemic Stroke.
Khounphinith, E, Yin, RX, Cao, XL, Huang, F, Wu, JZ, Li, H
International journal of medical sciences. 2019;(6):864-871
Abstract
Background: The T-cell immunoglobulin and mucin domain 4 gene (TIMD4) rs6882076 single nucleotide polymorphism (SNP) has been associated with serum total cholesterol, low-density lipoprotein cholesterol and triglycerides (TG) levels, but the results are inconsistent. Moreover, little is known about such association in Chinese populations. The aim of this study was to detect the association of the TIMD4 rs6882076 SNP and serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Southern Chinese Han population. Methods: Genotypes of the TIMD4 rs6882076 SNP in 1765 unrelated subjects (CHD, 581; IS, 559 and healthy controls, 625) were determined by the Snapshot Technology. Results: The genotypic and allelic frequencies of the TIMD4 rs6882076 SNP were different between the CHD/IS patients and controls (P < 0.05 for all). The subjects with CT/TT genotypes were associated with decreased risk of CHD (P = 0.014 for CT/TT vs. CC genotypes, P = 0.010 for T vs. C alleles) and IS (P = 0.003 for CT/TT vs. CC genotypes; P = 0.016 for T vs. C alleles). The T allele carriers in healthy controls were also associated with decreased levels of serum TG. Conclusions: The results of the present study suggest that the TIMD4 rs6882076 SNP is associated with decreased risk of CHD and IS in our study population. It is likely to decrease the CHD and IS risk by reducing serum TG levels.
-
4.
The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury: A prospective study.
Lyu, M, Zhou, J, Chen, H, Bai, H, Song, J, Liu, T, Cheng, Y, Ying, B
Medicine. 2019;(44):e17821
-
-
Free full text
-
Abstract
Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686-6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487-6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.
-
5.
Study of Family Clustering and PNPLA3 Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease.
Sood, V, Khanna, R, Rawat, D, Sharma, S, Alam, S, Sarin, SK
Indian pediatrics. 2018;(7):561-567
Abstract
OBJECTIVE To find association of pediatric NAFLD with metabolic risk factors, and Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene polymorphism. DESIGN Cross-sectional study. SETTING Pediatric Hepatology unit of a tertiary care hospital. PARTICIPANTS Overweight/obese children (<18 years) with (69 patients) or without (30 patients) NAFLD (ultrasonography based), and their parents. INTERVENTION Metabolic screening, PNPLA3 gene polymorphism, and transient elastography. OUTCOME MEASURE Association of pediatric NAFLD with parental metabolic risk factors and PNPLA3 gene polymorphism. RESULTS In the NAFLD group, there was high parental incidence of metabolic diseases, fatty liver (80%) and low high-density lipoproteins levels (84%). Family history of NAFLD (in any parent), higher alanine aminotransferase levels and higher total cholesterol levels in the child independently predicted possibility of NAFLD, but similar results could not be replicated for PNPLA3 gene polymorphism. Controlled attenuation parameter measurement (by transient elastography) had high sensitivity and specificity to diagnose steatosis. CONCLUSIONS There is high familial incidence of metabolic diseases in children with NAFLD. Controlled attenuation parameter can be useful as a non-invasive modality to screen fatty liver in children.
-
6.
Expanding spectrum of contactin-associated protein 2 (CASPR2) autoimmunity-syndrome of parkinsonism and ataxia.
Kannoth, S, Nambiar, V, Gopinath, S, Anandakuttan, A, Mathai, A, Rajan, PK
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(3):455-460
Abstract
Contactin-associated protein 2 (CASPR2) antibodies are originally associated with Morvan's syndrome and peripheral nerve hyper excitability. Our objective was to study retrospectively the clinical spectrum of CASPR2 antibody-positive patients in our hospital. This is a retrospective observational study. Patients treated at the Amrita Institute of Medical Sciences from May 2013 to April 2016, who were tested positive for CASPR2 antibodies, were included. A total of 1584 samples were tested in the neuroimmunology laboratory during the study period for voltage-gated potassium channel (VGKC) complex antibodies-leucine-rich glioma-inactivated protein 1 (LGI1) and CASPR2 antibodies. Thirty-four were positive for LGI1, 13 were positive for CASPR2, and 7 were for both (total 54-3.4% positivity). Of these 54 cases, 11 were treated in our hospital. Seven were positive for LGI1, three for CASPR2, and one for both. The patient who had both CASPR2 and LGI1 antibody positive had Morvan's syndrome. One patient with CASPR2 had neuromyotonia. The other patient was admitted with status epilepticus with a syndrome of parkinsonism and ataxia. The third patient had encephalopathy and myoclonus with a syndrome of parkinsonism and ataxia. Two of them underwent siddha treatment for other ailments prior to the onset of the disease for other ailments. Our short series shows the expanding spectrum of CASPR2 autoimmunity. Syndrome of parkinsonism and ataxia is an important manifestation of CASPR2 autoimmunity where we can offer a definitive treatment.
-
7.
An exploratory genome-wide analysis of genetic risk for alcoholic hepatitis.
Beaudoin, JJ, Long, N, Liangpunsakul, S, Puri, P, Kamath, PS, Shah, V, Sanyal, AJ, Crabb, DW, Chalasani, NP, Urban, TJ, et al
Scandinavian journal of gastroenterology. 2017;(11):1263-1269
-
-
Free full text
-
Abstract
OBJECTIVES To elucidate the genetic variability between heavy drinkers with and without alcoholic hepatitis (AH). MATERIALS AND METHODS An exploratory genome-wide association study (GWAS; NCT02172898) was conducted comparing 90 AH cases with 93 heavy drinking matched controls without liver disease in order to identify variants or genes associated with risk for AH. Individuals were genotyped using the multi-ethnic genotyping array, after which the data underwent conventional quality control. Using bioinformatics tools, pathways associated with AH were explored on the basis of individual variants, and based on genes with a higher 'burden' of functional variation. RESULTS Although no single variant reached genome-wide significance, an association signal was observed for PNPLA3 rs738409 (p = .01, OR 1.9, 95% CI 1.1-3.1), a common single nucleotide polymorphism that has been associated with a variety of liver-related pathologies including alcoholic cirrhosis. Using the improved gene set enrichment analysis for GWAS tool, it was shown that, based on the single variants' trait-association p-values, multiple pathways were associated with risk for AH with high confidence (false discovery rate [FDR] < 0.05), including several pathways involved in lymphocyte activation and chemokine signaling, which coincides with findings from other research groups. Several Tox Functions and Canonical Pathways were highlighted using Ingenuity Pathway Analysis, with an especially conspicuous role for pathways related to ethanol degradation, which is not surprising considering the phenotype of the genotyped individuals. CONCLUSION This preliminary analysis suggests a role for PNPLA3 variation and several gene sets/pathways that may influence risk for AH among heavy drinkers.
-
8.
Increased sclerostin and preadipocyte factor-1 levels in prepubertal rhythmic gymnasts: associations with bone mineral density, body composition, and adipocytokine values.
Jürimäe, J, Tillmann, V, Cicchella, A, Stefanelli, C, Võsoberg, K, Tamm, AL, Jürimäe, T
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2016;(3):1239-1243
Abstract
SUMMARY Rhythmic gymnastics as high-impact bone loading sport has positive effects on bone mineralization in prepubertal years. Sclerostin and preadipocyte factor-1 (Pref-1) are hormones that inhibit bone formation. The present study demonstrates that these hormones are higher in gymnasts, and gymnasts present higher bone mineral density (BMD) as compared to controls. INTRODUCTION Rhythmic gymnasts (RG) start their heavy trainings already in prepuberty and despite of low body fat mass (FM) and hypoleptinemia, their BMD is higher than in non-trained normal girls. The specific role of sclerostin and Pref-1, which are the inhibitors of bone formation, in bone development is not well understood. The impact of sclerostin and Pref-1 levels on BMD, body composition, and adipocytokine values was studied in prepubertal RG and untrained controls (UC). METHODS Sixty-four 9-10-year-old girls were divided into RG (n = 32) and UC (n = 32) groups. Bone mineral and body composition values were measured by dual-energy X-ray absorptiometry and bone age by X-ray. Sclerostin, Pref-1, leptin, and adiponectin levels were measured from fasting blood samples. RESULTS Sclerostin (RG 19.8 ± 6.3 pmol/l; UC 15.8 ± 5.4 pmol/l) and Pref-1 (RG 1.6 ± 1.0 ng/ml; UC 1.1 ± 0.5 ng/ml) were higher (p < 0.05) in RG compared with UC. Sclerostin was related to adiponectin (r = 0.41; p < 0.05) in UC. No relationship was found between sclerostin and Pref-1 with BMD values in prepubertal RG and age-matched UC groups. CONCLUSIONS Sclerostin and Pref-1 levels are higher in RG compared to UC girls. Specific physical activity pattern seen in prepubertal RG has a beneficial effect on bone mineralization despite increased levels of hormones that inhibit bone formation.
-
9.
The prognostic value of serum signal peptide-Cub-Egf domain-containing protein-1 concentrations in acute intracerebral hemorrhage.
Qiu, SZ, Wang, HX, Shen, J, Zheng, GR, Chen, B, Huang, JJ, Gao, JB
Clinica chimica acta; international journal of clinical chemistry. 2016;:103-9
Abstract
BACKGROUND Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1) in peripheral blood, which is identified as a marker for coagulation, was reported to be an independent predictor of poor outcome in some illnesses. We investigated the clinical utility of serum SCUBE1 in the prognosis of intracerebral hemorrhage (ICH). METHODS A total of 128 consecutive patients, admitted to emergency service due to acute ICH, and 128 healthy individuals were included in this prospective study. The patients were followed up until 6months or death. An unfavorable outcome was defined as modified Rankin Scale score>2. RESULTS Serum SCUBE1 concentration was markedly higher in patients than in controls and was associated with hematoma volume, National Institutes of Health Stroke Scale (NIHSS) score and blood platelet count. After adjustment for hematoma volume and NIHSS score, it was still related to early neurological deterioration, hematoma growth, 1-week mortality, 6-month mortality, 6-month unfavorable outcome and 6-month overall survival. Additionally, serum SCUBE1 significantly improved areas under receiver operating characteristic curve of hematoma volume and NIHSS score to predict 6-month unfavorable outcome. CONCLUSIONS Increased serum SCUBE1 concentrations have close relation to increasing severity and poor prognosis of ICH.
-
10.
Age-dependent ferritin elevations and HFE C282Y mutation as risk factors for symptomatic knee osteoarthritis in males: a longitudinal cohort study.
Kennish, L, Attur, M, Oh, C, Krasnokutsky, S, Samuels, J, Greenberg, JD, Huang, X, Abramson, SB
BMC musculoskeletal disorders. 2014;:8
Abstract
BACKGROUND Age, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role. METHODS In a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods. RESULTS Higher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86-27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023). CONCLUSION Our data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.