The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease.

BACKGROUND: Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. METHODS: In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P > .05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P = .036, odds ratio = 2.09 [95% CI = 1.31-5.95]). CONCLUSIONS: We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.

Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease.

Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (-202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Serum Alkaline Phosphate Level Associates with Metabolic Syndrome Components Regardless of Non-Alcoholic Fatty Liver; A Population-Based Study in Northern Iran.

Background: Serum alkaline phosphatase (ALP) is an indicator of hepatobiliary disorders, such as metabolic syndrome (MetS). To assess the association between serum ALP levels and MetS, with or without non-alcoholic fatty liver disease (NAFLD), in a cohort study in northern Iran. Methods: Data from approximately 5257 subjects aged more than 18 years participating in the Amol cohort were used. We extracted the required data and investigated the correlation between liver enzyme levels and MetS. Multiple logistic regression analyses based on the serum ALP quartiles were performed. Results: Of them, 2860 were male with a mean age of 42.11±16.1 years. A positive linear trend was observed between serum ALP levels and the number of MetS components in both sexes. In both sexes, systolic blood pressure, waist circumferences, and high-density lipoprotein (HDL) had a significant association with ALP. After adjusting for age, both sexes with NAFLD showed an increased risk of developing MetS. The risk of NAFLD increased in individuals with>2nd quartile of ALP. Furthermore, higher ALP levels were associated with an increased risk of MetS in males (1.1014 [0.782-1.315]) and females (1.441 [1.085-1.913]). Conclusion: There is a significant association between serum ALP levels and MetS, independent of fatty liver changes, suggesting that this marker can be considered as a feasible predictor of MetS.

Insulin receptor substrate 2 gene Gly1057Asp polymorphism is a risk factor for nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), which is an emerging global chronic liver disease, has a close association with insulin resistance. We aimed to determine whether the Gly1057Asp (rs1805097) polymorphism of the insulin receptor substrate 2 (IRS2) gene is associated with NAFLD. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism method, 135 patients with biopsy-proven NAFLD and 135 controls underwent IRS2 genotype analysis. RESULTS: Genotype and allele distributions of the IRS2 gene Gly1057Asp variant conformed to the Hardy-Weinberg equilibrium in both the case and control groups (P > .05). The Asp/Asp genotype of IRS2 gene Gly1057Asp polymorphism compared with Gly/Gly genotype was associated with a 2.1-fold increased risk for NAFLD after adjustment for confounding factors (P = .029; odds ratio = 2.10, 95% CI = 1.23-3.97). CONCLUSION: Our findings revealed for the first time that the Gly1057Asp Asp/Asp genotype of the IRS2 gene is a marker of increased NAFLD susceptibility; however, studies in other populations are required to confirm the results.

A visfatin gene promoter polymorphism (rs1319501) is associated with susceptibility to nonalcoholic fatty liver disease.

Background: Considering the role of visfatin in nonalcoholic fatty liver disease (NAFLD), a growing global epidemic, this article explores the potential association between the visfatin gene (NAMPT) and NAFLD. Methods: We used the PCR-restriction fragment length polymorphism method to genotype the rs1319501 promoter variant of the NAMPT gene in 154 patients with biopsy-proven NAFLD and 158 controls in this case-control genetic association study. Results: The 'CC+TC' genotype of NAMPT rs1319501 in comparison to the 'TT' genotype occurred less frequently in the cases with NAFLD than the controls, and the difference remained significant after adjustment for confounding factors (p = 0.029; odds ratio = 0.55; 95% CI = 0.31-0.82). Conclusion: This study showed, for the first time, that the carriers of the NAMPT rs1319501 'CC+TC' genotype had a 45% decreased risk for NAFLD.

The common variant of rs6214 in insulin like growth factor 1 (IGF1) gene: a potential protective factor for non-alcoholic fatty liver disease.

PURPOSE: Regarding the central role of insulin resistance in NAFLD, we explored whether insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein 3 (IGFBP3) gene variants were associated with NAFLD susceptibility. METHODS: IGF1 (rs6214) and IGFBP3 (rs3110697) gene variants were genotyped in 154 cases with biopsy-proven NAFLD and 156 controls using PCR-RFLP method. RESULTS: The IGF1 rs6214 "AA + AG" genotype compared with the "GG" genotype appeared to be a marker of decreased NAFLD susceptibility (p = .006; OR = 0.47, 95%CI = 0.28-0.80). Furthermore, the IGF1 rs6214 "A" allele was underrepresented in the cases than controls (p = .024; OR = 0.61, 95%CI = 0.40-0.94). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for IGFBP3 gene. CONCLUSIONS: To our knowledge, these findings suggest, for the first time, that the IGF1 rs6214 "A" allele and "AA + AG" genotype have protective effects for NAFLD susceptibility. Nonetheless, further studies are needed to validate our findings.

RESISTIN GENE POLYMORPHISM AND NONALCOHOLIC FATTY LIVER DISEASE RISK.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. METHODS: A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. RESULTS: NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P<0.001). However, we observed no significant difference in genotype and allele frequencies between the cases with NAFLD and the controls for the RETN rs3745367 polymorphism either before or after adjustment for confounding factors including age, BMI, sex, smoking status, SBP, and DBP. CONCLUSION: To our knowledge, this study is the first one that investigated the association between RETN gene rs3745367 variant and biopsy-proven NAFLD. Our findings do not support a role for this gene polymorphism in NAFLD risk in Iranian population; nonetheless, they need to be further investigated in other populations.

Risco de polimorfismo genético resistina e doença hepática gordurosa não alcoólica / Resistin gene polymorphism and nonalcoholic fatty liver disease risk

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and one of the main global health issues in which liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Owing to the link between NAFLD and insulin resistance (IR) and obesity and the role of resistin in theses metabolic disorders, we explored the possible association between resistin gene (RETN) variant and NAFLD. Methods A total of 308 unrelated subjects, including 152 patients with biopsy-proven NAFLD and 156 controls were enrolled and genotyped for the RETN gene rs3745367 variant using PCR-RFLP method. Results NAFLD patients had higher liver enzymes, systolic blood pressure (SBP), and diastolic blood pressure (DBP) than the controls (P<0.001). However, we observed no significant difference in genotype and allele frequencies between the cases with NAFLD and the controls for the RETN rs3745367 polymorphism either before or after adjustment for confounding factors including age, BMI, sex, smoking status, SBP, and DBP. Conclusion To our knowledge, this study is the first one that investigated the association between RETN gene rs3745367 variant and biopsy-proven NAFLD. Our findings do not support a role for this gene polymorphism in NAFLD risk in Iranian population; nonetheless, they need to be further investigated in other populations.

RESUMO Contexto: A doença hepática gordurosa não alcoólica (DHGNA) é uma doença hepática crônica e um dos principais problemas de saúde global em que a gordura hepática ultrapassa 5% dos hepatócitos sem as causas secundárias de acúmulo lipídico ou consumo excessivo de álcool. Devido à ligação entre a DHGNA e resistência à insulina (IR) e obesidade e o papel da resistina em distúrbios metabólicos, exploramos a possível associação entre a variante do gene resistina (RETN) e a DHGNA. Metodos Foram selecionados 308 indivíduos não relacionados, incluindo 152 pacientes com DHGNA comprovada por biópsia e 156 controles para a variante do gene RETN rs3745367 usando o método PCR-RFLP. Resultados Pacientes com DHGNA apresentaram enzimas hepáticas mais elevadas, assim como pressão arterial sistólica e pressão arterial diastólica maiores do que os controles (P<0,001). No entanto, não se observou diferença significativa nas frequências genótipo e alelo entre os casos com DHGNA e os controles para o polimorfismo RETN rs3745367 antes ou depois do ajuste para fatores de confusão, incluindo idade, índice de massa corporal, sexo, estado de tabagismo, pressão arterial sistólica e pressão arterial diastólica. Conclusão Para nosso conhecimento, este estudo foi o primeiro que investigou a associação entre a variante do gene RETN rs3745367 e a DHGNA comprovada em biópsia. Nossas descobertas não suportam um papel para este polimorfismo genético no risco DHGNA na população iraniana; no entanto, eles precisam ser mais investigados em outras populações.

Association of rs5742612 Polymorphism in the Promoter Region of IGF1 Gene with Nonalcoholic Fatty Liver Disease: A Case-Control Study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease encompassing a wide spectrum of disorders ranging from simple steatosis to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Considering the strong association between NAFLD and insulin resistance, and the vital role of insulin-like growth factor 1 (IGF1) in IR, we hypothesized that IGF1 gene polymorphism might be associated with NAFLD. METHODS: A total of 302 subjects, including 149 patients with biopsy-proven NAFLD and 153 controls, were enrolled in this case-control study. All the subjects were genotyped for the rs5742612 polymorphism of the IGF1 gene using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The distribution of IGF1 rs5742612 genotypes and alleles differed significantly between the cases with NAFLD and controls. The IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype occurred more frequently in the cases than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (P = .011, OR = 2.71, 95%CI = 1.16-5.85; and P = .032, OR = 2.29, 95% CI = 1.10-5.24, respectively). CONCLUSION: For the first time, this study uncovered that the IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype had a 2.71-fold or 2.29-fold increased risk for NAFLD, respectively.

CIRCULATING GHRELIN LEVELS AND SUSCEPTIBILITY TO COLORECTAL CÂNCER.

BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 controls were enrolled in this study. Plasma levels of ghrelin, insulin, and glucose were measured in all the subjects using ELISA and glucose oxidase methods. Furthermore, insulin resistance was assessed by calculating HOMA-IR index. RESULTS: The cases with CRC had decreased ghrelin levels (P<0.001) and a higher HOMA-IR index (P<0.001) than controls. Interestingly, when CRC patients were stratified based on tumor site, lower ghrelin levels and a higher HOMA-IR index were observed in the patients with either colon or rectal cancer vs. controls too. Additionally, there were an age and BMI-independent negative correlation between ghrelin levels and HOMA-IR (r=-0.365, P<0.05), and an age-independent negative correlation between ghrelin levels and BMI (r=-0.335, P<0.05) in the rectal subgroup. CONCLUSION: Our findings support a role for ghrelin in connection with insulin resistance and obesity in CRC susceptibility; however, it needs to be corroborated by further studies.

The "GG" genotype of rs26802 variant in the ghrelin gene is a potential protective factor against nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD. METHODS: We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method. RESULTS: The GHRL rs26802 "GG" genotype compared with the "TT" genotype and "TT+TG" genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03-0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05-0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169. CONCLUSIONS: These findings proposed, for the first time, that the GHRL rs26802 "GG" genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.

Níveis de grelina circulante e a suscetibilidade ao câncer colorretal / Circulating ghrelin levels and susceptibility to colorectal câncer

ABSTRACT BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 controls were enrolled in this study. Plasma levels of ghrelin, insulin, and glucose were measured in all the subjects using ELISA and glucose oxidase methods. Furthermore, insulin resistance was assessed by calculating HOMA-IR index. RESULTS: The cases with CRC had decreased ghrelin levels (P<0.001) and a higher HOMA-IR index (P<0.001) than controls. Interestingly, when CRC patients were stratified based on tumor site, lower ghrelin levels and a higher HOMA-IR index were observed in the patients with either colon or rectal cancer vs. controls too. Additionally, there were an age and BMI-independent negative correlation between ghrelin levels and HOMA-IR (r=-0.365, P<0.05), and an age-independent negative correlation between ghrelin levels and BMI (r=-0.335, P<0.05) in the rectal subgroup. CONCLUSION: Our findings support a role for ghrelin in connection with insulin resistance and obesity in CRC susceptibility; however, it needs to be corroborated by further studies.

RESUMO CONTEXTO E OBJETIVO: Considerando a associação entre câncer colorretal (CCR), a resistência à insulina, à obesidade e o papel proeminente da grelina nessas doenças metabólicas, foi explorado se os níveis plasmáticos de grelina estavam associados ao CCR. Além disso, nos pacientes com CCR foram pesquisadas as possíveis correlações entre a grelina, insulina, resistência insulínica e índice de massa corporal (IMC) como indicadores de obesidade. MÉTODOS: Foram incluídos neste estudo 170 indivíduos, sendo 82 com CRC e 88 controles. Os níveis plasmáticos de grelina, insulina e glicose foram medidos em todos os sujeitos utilizando métodos ELISA e glicose oxidase. Além disso, a resistência à insulina foi avaliada pelo cálculo do índice HOMA-IR. RESULTADOS: Os pacientes com CRC apresentaram redução dos níveis de grelina (P<0,001) e maior índice HOMA-IR (P<0.001) do que os controles. Curiosamente, quando os pacientes com CRC foram estratificados com base no local do tumor, níveis mais baixos de grelina e maior índice de HOMA-IR foram observados nos indivíduos com câncer de cólon ou retal versus controles também. Além disso, houve uma correlação negativa entre idade e IMC independente entre os níveis de grelina e HOMA-IR (r=-0,365, P<0,05) e uma correlação negativa independente da idade entre os níveis de grelina e IMC (r=-0,335, P<0,05) no subgrupo retal. CONCLUSÃO: Nossos achados apoiam o papel da grelina em relação à resistência à insulina e à obesidade na suscetibilidade do CRC; no entanto, ela precisa ser corroborada por estudos posteriores.

The Leu72Met (rs696217 G>T) Polymorphism of the Ghrelin Gene Might Be a Protective Factor for Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing problem and the commonest cause of chronic liver disease throughout the world. Given the strong association between NAFLD and insulin resistance and obesity, as well as the central role of ghrelin in these metabolic disorders, we explored whether ghrelin (GHRL) and ghrelin receptor (GHSR) gene polymorphisms were associated with susceptibility to NAFLD. METHODS: In this case-control retrospective study which was conducted between April 2010 and July 2013, GHRL (rs696217 or Leu72Met) and GHSR (rs2922126) gene polymorphisms were genotyped in 153 cases with biopsy-proven NAFLD and 157 controls using the polymerase chain reaction - restriction fragment length polymorphism method. RESULTS: The GHRL rs696217 "GT+TT" genotype or "GT" genotype compared with the "GG" genotype occurred less frequently in the patients with NAFLD than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (p=0.018; OR=0.35, 95%CI: 0.14-0.84 and p=0.046; OR=0.40, 95%CI: 0.16-0.98, respectively). Furthermore, the GHRL rs696217 'T' allele compared with 'G' allele was significantly underrepresented in the cases (p=0.007; OR=0.33, 95%CI: 0.15-0.76). Nevertheless, no significant difference was found for GHSR rs2922126 gene polymorphism. CONCLUSIONS: Our findings suggested, for the first time, that the GHRL rs696217 or Leu72Met "GT+TT" genotype and "GT" genotype compared with "GG" genotype, as well as the "T" or Met72 allele compared with "G" or Leu72 allele had a protective effect for NAFLD susceptibility. However, other studies are required to confirm these findings.

Relationship between dietary macronutrient composition and non-alcoholic fatty liver disease in lean and non-lean populations: a cross-sectional study.

OBJECTIVE: The current study aimed to customize dietary changes for lean patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: The current study was done with a population-based cross-sectional design. The FFQ was used to analyse dietary macronutrient intake and ultrasonography results for NAFLD diagnosis. The study subjects were divided into the lean and non-lean groups based on their BMI (< 25 and ≥ 25). Multivariable logistic regression was used to evaluate the relationship between dietary macronutrients and NAFLD. Substitution analyses were also performed. SETTING: Amol and its suburban areas in Iran. PARTICIPANTS: Adults in the age range of 18 to < 65 with full relevant data. RESULTS: Among the total study subjects (2308), 46·7 % had fatty liver. The substitution of polysaccharides for animal protein and SFA in the lean group resulted in a significant NAFLD reduction, whereas the substitution of SFA for all types of macronutrients, except for n-6 and mono-disaccharides, led to a significant increase in NAFLD (P < 0·05). In non-lean participants, the substitution of MUFA for mono-disaccharides resulted in a significant reduction of NAFLD (P < 0·05). In this group, the substitution of SFA and mono-disaccharides for MUFA, and n-6 for all macronutrients, except vegetable protein and SFA, were significantly related to an increase in NAFLD (P < 0·05). CONCLUSIONS: Lower lean NAFLD is correlated with increasing polysaccharides in exchange for SFA and animal protein intake, whereas lower non-lean NAFLD is correlated with increasing MUFA in exchange for mono-disaccharides and reducing n-6 and SFA.

INSULIN AND INSULIN RECEPTOR GENE POLYMORPHISMS AND SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. OBJECTIVE: Given the pivotal role of insulin resistance in NAFLD, we hypothesized that insulin (INS) and insulin receptor (INSR) gene polymorphisms may be associated with NAFLD risk. METHODS: A total of 312 subjects, including 153 cases with biopsy-proven NAFLD and 159 controls were enrolled in this case-control study. Four polymorphisms in INS (rs3842752, rs689) and INSR (rs1052371, rs1799817) genes were genotyped using PCR-RFLP method. RESULTS: The cases with NAFLD were older and had higher BMI, systolic blood pressure, diastolic blood pressure, as well as higher serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase than the controls (P<0.001). The "TT" genotype of INSR rs1799817 compared with "CC" genotype occurred more frequently in the controls than the cases with NAFLD and the difference remained significant after adjustment for confounding factors (P=0.018; OR=0.10, 95%CI=0.02-0.76). However, no significant difference was found for INS rs3842752, INS rs689, and INSR rs1052371 gene polymorphisms between the cases with NAFLD and the controls either before or after adjustment for the confounders. CONCLUSION: These findings corroborate the hypothesis that genetic polymorphisms related to insulin resistance play a role in NAFLD susceptibility. Specifically, the INSR rs1799817 "TT" genotype had a protective effect for NAFLD. However, our results remain to be validated in other studies.

Insulina e polimorfismos do gene do receptor de insulina e a suscetibilidade à doença hepática gordurosa não alcoólica / Insulin and insulin receptor gene polymorphisms and susceptibility to nonalcoholic fatty liver disease

ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. OBJECTIVE: Given the pivotal role of insulin resistance in NAFLD, we hypothesized that insulin (INS) and insulin receptor (INSR) gene polymorphisms may be associated with NAFLD risk. METHODS: A total of 312 subjects, including 153 cases with biopsy-proven NAFLD and 159 controls were enrolled in this case-control study. Four polymorphisms in INS (rs3842752, rs689) and INSR (rs1052371, rs1799817) genes were genotyped using PCR-RFLP method. RESULTS: The cases with NAFLD were older and had higher BMI, systolic blood pressure, diastolic blood pressure, as well as higher serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase than the controls (P<0.001). The "TT" genotype of INSR rs1799817 compared with "CC" genotype occurred more frequently in the controls than the cases with NAFLD and the difference remained significant after adjustment for confounding factors (P=0.018; OR=0.10, 95%CI=0.02-0.76). However, no significant difference was found for INS rs3842752, INS rs689, and INSR rs1052371 gene polymorphisms between the cases with NAFLD and the controls either before or after adjustment for the confounders. CONCLUSION: These findings corroborate the hypothesis that genetic polymorphisms related to insulin resistance play a role in NAFLD susceptibility. Specifically, the INSR rs1799817 "TT" genotype had a protective effect for NAFLD. However, our results remain to be validated in other studies.

RESUMO CONTEXTO: A doença hepática gordurosa não alcoólica (NAFLD) é uma preocupação global crescente da saúde definida pelo excesso de teor de gordura hepática na ausência de consumo excessivo de álcool. OBJETIVO: Dado o papel crucial da resistência à insulina no NAFLD, criou-se a hipótese de que os polimorfismos genéticos da insulina (INS) e do receptor de insulina (INSR) podem estar associados ao risco de NAFLD. MÉTODOS: Um total de 312 indivíduos, incluindo 153 casos com NAFLD comprovado por biópsia e 159 controles foram inscritos neste estudo de caso-controle. Quatro polimorfismos em genes INS (rs3842752, rs689) e INSR (rs1052371, rs1799817) foram genotipados utilizando o método PCR-RFLP. RESULTADOS: Os casos com NAFLD foram mais idosos e apresentaram maior IMC, pressão arterial sistólica, pressão arterial diastólica, bem como níveis séricos mais elevados de aspartato aminotransferase, de alanina aminotransferase e de gama glutamil transpeptidase do que os controles (P<0,001). O genótipo "TT" de INSR rs1799817 em comparação com o genótipo "CC" ocorreu com mais frequência nos controles do que os casos com NAFLD e a diferença permaneceu significativa após ajuste para fatores de confusão (P=0,018; OR=0,10, IC95%=0,02-0,76). No entanto, não foi encontrada diferença significativa para INS rs3842752, INS rs689 e INSR rs1052371 polimorfismos genéticos entre os casos com NAFLD e os controles antes ou depois do ajuste para os fatores de confusão. CONCLUSÃO: Esses achados corroboram a hipótese de que os polimorfismos genéticos relacionados à resistência à insulina desempenham um papel na suscetibilidade do NAFLD. Especificamente, o genótipo INSR rs1799817 "TT" teve um efeito protetor para o NAFLD. No entanto, nossos resultados necessitam ser validados em outros estudos.

Insulin Resistance and Colorectal Cancer Risk: the Role of Elevated Plasma Resistin Levels.

PURPOSE: Given the important role of resistin in insulin resistance (IR) and obesity, as well as the associations between both IR and obesity and increased risk of colorectal cancer (CRC), we investigated whether plasma resistin levels were associated with CRC risk. Furthermore, the possible correlations between resistin and insulin, IR, and obesity in patients with CRC and controls were explored. METHODS: This study was conducted as a case-control study and 170 subjects, including 88 controls and 82 cases with CRC, were enrolled and their plasma levels of glucoe, insulin, and resistin were measured using glucose oxidase or ELISA methods. Moreover, IR was calculated according to HOMA-IR index. RESULTS: The cases with CRC had a higher HOMA-IR than the controls (1.8 ± 0.4 versus 1.4 ± 0.3, P < 0.001). Additionally, after the stratification of the cases with CRC by tumor site, higher levels of resistin and insulin, and a higher HOMA-IR in the cases with rectal cancer than in the controls were observed (resistin 5.9 ± 1.2 versus 5.4 ± 1.3, P = 0.043; insulin 5.9 ± 1.2 versus 5.4 ± 1.3, P = 0.039; HOMA- IR 1.9 ± 0.4 versus 1.3 ± 0.3, P < 0.001). Furthermore, resistin was positively correlated with insulin in the controls (r = 0.737, P < 0.001), the cases with CRC (r = 0.881, P < 0.001), the cases with colon cancer (r = 0.811, P < 0.001), and the cases with rectal cancer (r = 0.990, P < 0.001). All these differences remained significant after adjustment for confounding factors. CONCLUSIONS: The findings of the present study reinforce the hypothesis that higher plasma levels of resistin in connection with insulin resistance play a role in susceptibility to colorectal, notably rectal, cancer. Nevertheless, further studies with bigger sample sizes are required to validate these findings.

Association between Pattern of Gastritis and Gastroesophageal Reflux Disease in Patients with Helicobacter Pylori Infection.

BACKGROUND Reflux disease is a common gastrointestinal problem. The association between reflux disease and gastritis pattern is controversial. AIM: To determine the association between reflux disease and gastritis pattern in patients with Helicobacter pylori (H. pylori) infection. METHODS 470 patients with dyspepsia and reflux disease were enrolled in this study. The inclusion criteria were willing to participate in the study, age over 40 years, and having the criteria of ROME III for at least 3 months. Patients with history of H. pylori eradication therapy during the 3 months before the study, a history of gastric surgery, and gastric cancer were excluded. All of the participants underwent upper endoscopy and two biopsy samples were taken from antrum, body, and fundal areas. RESULTS H. pylori infection rate was 367 (78.1%) with mean age of 59.8 ± 11.4 years. Of them 131 patients (35.7%) were male. Reflux disease was detected in 273 (74.4%) patients. 216 (58.9%) and 102 (27.8%) patients had non-erosive reflux disease (NERD) and gastroesophageal reflux disease (GERD), respectively. Corpus predominant and antral predominant gastritis were seen in 72 (19.6%) and 129 (35.2%) patients, respectively. Antral gastritis was significantly associated with GERD (p<0.01). In regression analysis, antral predominant gastritis had a significant association with GERD (OR=1.92; 95%CI: 1.22- 3.12). The same result was observed in mild to moderate antral and greater curvature gastritis (OR= 1.26; 95%CI: 0.25-6.40 and OR= 3.0; 95%CI: 0.63-14.17, respectively). CONCLUSION According to these finding ,we could suggest that the pattern of gastritis could be associated with reflux disease and GERD.

Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity.

BACKGROUND: Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality around the world. OBJECTIVES: With regard to the role of obesity in colorectal cancer (CRC) and the role of leptin in obesity, we investigated whether leptin (LEP) and leptin receptor (LEPR) gene variants are associated with CRC risk. PATIENTS AND METHODS: We evaluated LEP (rs7799039) and LEPR (rs1137101) gene variants by using PCR-RFLP method in 261 cases with CRC and 339 controls. RESULTS: No significant difference was found for rs7799039 and rs1137101gene variants between the cases with CRC and controls. However, the LEPR rs1137101 "GG" genotype compared with "AA" genotype and "AA + AG" genotype was associated with increased risks for obesity, and the differences remained significant after adjustment for confounding factors including age, sex, smoking status, and NSAID use (P = 0.015; OR = 2.42, 95%CI = 1.19 - 4.93 and P = 0.016; OR = 2.28, 95%CI = 1.17 - 4.48, respectively). In addition, the LEPR "G" allele compared with the "A" allele was associated with an increased risk for obesity (P = 0.024; OR = 1.44, 95%CI = 1.05 - 1.98). CONCLUSIONS: Consistent with most previous studies, our findings found no association between LEP (rs7799039) and LEPR (rs1137101) gene variants and CRC risk. However, the LEPR rs1137101 "GG" genotype compared with the "AA" genotype and "AA+AG" genotype was associated with a 2.42-fold and a 2.28-fold increased risk for obesity, respectively.