GSTM1 and GSTT1 gene deletions in causing predisposition to adult ALL.Biotransformation of xenobiotics are critical for their metabolism and removal from the body which is carried out by xenobiotic metabolizing enzymes. Individuals carrying variants of genes that encode these enzymes have an altered ability to metabolize xenobiotics which may lead to an increased risk of acute lymphoblastic leukemia. The current study aimed to investigate the impact of GSTM1 and GSTT1 deletions. The genotype frequency obtained for patients was compared to controls using odds ratio and chi-square.The current case-control study involved 62 adult ALL patients and 62 age and gender matched healthy controls. Whole blood samples processed with standard phenol chloroform protocol for DNA isolation were genotyped using multiplex PCR approach for simultaneous identification of GSTM1 and GSTT1 in a group of adult ALL patients from Pakistan were 47% and 11% respectively. Deletion of GSTM1 and GSTT1 did not show statistically significant association with adult ALL (p=0.86 and p=0.35 respectively). The combined GSTM1/GSTT1 deletion was observed in 2% patients and was not significantly associated with ALL in adults (p=0.85).The null genotype frequency of GSTM1 and GSTT1genes does not influence ALL susceptibility among adult patients. Cancer susceptibility associated with GST polymorphism varies with ethnic and geographic differences. Therefore, further investigation on different populations is needed to understand the role of these genetic variations in modifying adult ALL risk.The results reveal that homozygous null polymorphism of  Acute lymphoblastic leukemia (ALL) is a blood malignancy distinguished by an excessive buildup of lymphoid progenitor cells in blood and bone marrow. ALL constitutes one fourth of all cancer cases occurring in childhood making it the most common pediatric cancer.5The development of ALL includes both genetic and environmental factors with DNA damage in hematopoietic precursor cells being acrucial step.GSTM1 and GSTT1, exhibit null polymorphism indicating homozygous deletion of the genes.GST deletion has also been studied in the development of hematologic malignancies.GSTM1 and GSTT1among adult ALL patients in comparison to controls was studiedand their association with the occurrence of adult ALL was examined.The glutathione S-transferases (GSTs) constitute an enzyme super family responsible for detoxification of carcinogens. Detoxification represents the second phase of carcinogen metabolism in human body, followed by bioactivation of procarcinogens (phase I). GSTs detoxify reactive intermediates produced during the first phase of metabolism by conjugating soluble glutathione with them.The current case control study was assessed and ethically approved by the Institutional Ethical Committee of the Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi. The study comprised 62 adult ALL cases and an equal number of controls. Patients were recruited from department of oncology, Jinnah Postgraduate Medical Centre (JPMC) Karachi, Pakistan after clinical diagnosis. Questionnaire was filled to collect personal information of patients while medical records were checked to extract their clinical history. Patients with history of other cancers were excluded. Healthy individuals from the population qualified as controls and were matched to cases on age and gender. All participants were provided with an information sheet explaining study objective along with potential risks and benefits associated with their participation prior to their enrolment in this study. A written informed consent declaring their voluntary participation was obtained from them.Five ml of whole blood was withdrawn from patients as well as controls in sterile acid citrate dextrose (ACD) vacutainer for genotype analysis. Collected blood samples were stored at -20°C till further use. They were treated with standard phenol chloroform procedure for genomic DNA isolation.GSTM1 and GSTT1genes.GSTM1, 5′ TTCCTTACTGGTCCTCACATCTC 3′ and 5′ TCACCGGATCATGGCCAGCA 3′ for GSTT1which resulted in 219bp and 459bp fragments respectively. β-globin gene was indicative of successful PCR. Primers used for its amplification were 5′ CAACTTCATCCACGTTCACC 3′ and 5′ GAAGAGCCAAGGACAGGTAC 3′ that gave a 268bpamplified product. Multiplex PCR was carried out with 200ng extracted DNA in total reaction volume of 20 µl. The other PCR componentsincluded 1x (NH4)2SO4 buffer, 1.5mM MgCl2, 200 μM dNTPs mix, 1.5 units of Taq DNA polymerase, 0.6 μM of sense and antisense primer for GSTM1, 0.3 μM of each primer for GSTT1 and 0.4 μM of each primer for β globin gene.PCR cycle conditions included an initial melting step at 94°C for four minutes, 35 PCR cycles, each including 30 s denaturation at 94°C, 35 s annealing at 58°C and 30 s elongation at 72°C, followed by a seven minutes long final elongation step at 72°C. Eight microliters ofthe PCRproducts were loaded on 2.5% agarose gel and electrophoresis was carried outfor 40 min at 100 V. The ethidium bromide stained gel containing amplified fragments wasvisualized under gel documentation system.Multiplex PCR assay was used to screen out homozygous deletions in GSTM1 and GSTT1for the disease. Chi-square test was performed to test association of homozygous deletion in GSTM1 and GSTT1 genes with development of adult ALL using VassarStats, a freely available online tool, under the null hypothesis of “no association”.16Odds ratio (OR) with 95% confidence interval (CI) was calculated to measure the risk conferred by null allele of The present study involved 62 adult ALL patients ranging from 15 to 55 years of age. The mean age (±SD) of patients at diagnosis was24.7 ± 1.1 years. Patients under 25 years of age constituted 53% of the total number of cases while 89% of patients were less than 35 years. Patients included both genders but male cases predominated female cases with a ratio of 2.4:1.GSTM1 and GSTT1 null polymorphism resulted in banding pattern shown in GSTM1deletion resulted in the absence of 219bp amplified product while absence of 459bp fragment meant homozygous deletion ofGSTT1gene. Amplification of β-globin gene resulting in 268bp fragment confirmed the success of PCR when both GST genes were deleted.Multiplex PCR assay for co-identification of GSTT1 null genotype (MlT0); lane 2, GSTM1 null and GSTT1 null genotype (M0T0); lane 3, 8, 9 and 10, GSTM1 null genotype (M0T1); lane 4, 5, 6, 7, 11, 12, GSTM1 and GSTT1 wild type genotype (M1T1)Lane M: 50 bp DNA ladder; lane 1, GSTM1 and GSTT1genes among patients and controls and the odds of their association with ALL are shown in GSTM1 and GSTT1 deletion among study participants (n=124) was46% and 8.7% respectively. GSTM1 was deleted in 47% adult ALL patients (n=62) and in 45% controls (n=62). The null genotype of GSTT1 was 11% for cases and 6% for healthy individuals. The Pearson chi-square test revealed neither GSTM1 deletion nor GSTT1 null genotype was significantly associated with adult ALL . GSTM1 and GSTT1 were simultaneously deleted in 1.6% cases as compared to 3.2% controls .Frequency distribution of homozygous null polymorphism in controls . This diGSTM1 and GSTT1 resulting from homozygous deletion of the respective genes lead to the lack of active enzymes. This loss of enzyme activity affects metabolism of several carcinogens and may therefore influence an individual’s risk of cancer development.GST genetic variants are also good candidates for association studies in leukemia as they have a potential to alter metabolism of leukemogens and to cause lack of protection against ROS leading to cellular DNA damage.17Glutathione S-transferases take part in detoxification of different carcinogens, environmental toxins and chemotherapeutic drugs. The null genotypes of GSTM1 and GSTT1deletions as predisposing factor of adult ALL revealed that the genotype frequencies of both genes were not significantly higher in ALL patients as compared to healthy controls (47% vs. 45% for GSTM1 and 11% vs. 6% for GSTT1). The use of healthy controls over hospital based controls was intentionally preferred to reduce possible bias in results due to the risk conferred by deletion polymorphism of GSTM1 and GSTT1to non-cancer diseases.The current study evaluating the impact of GST allelesis not uniform across human population and ethnic as well as geographic variations have been observed. In Asians, the frequency of GSTM1deletionhas been reported to vary between 42% and 54% (n=1511) while 35% to 52% for GSTT1 null polymorphism (n=575).GSTM1 and GSTT1 deletion to be 45% and 21% in Iranian (n=229) while 33% and 18% in North Indian (n=198) population respectively.20Distribution of Indian n=8 populatGSTM1 null polymorphism  or GSTT1 gene deletion  with ALL among adults. Most genetic association studies examining role of GSTM1 and GSTT1 deletion as a modulator of ALL risk have focused children affected with ALL. Only a limited number of studies have evaluated this risk with adult ALL owing to the fact that ALL has a higher occurrence in children as compared to adults. A study evaluating 71 adult ALL patients for GSTM1 and GSTT1 reported significant association of GSTT1 null variant  with adult ALL but no association of GSTM1 null genotype. The participants of this study were Caucasians.GSTM1 null genotype but were contradictory for GSTT1 as they showed negative association of GSTT1 deletion with ALL .GSTM1 or GSTT1 null genotype with ALL. The results of this study are comparable to our findings, however, the patients included in the study were all under 25 years of age.GST null polymorphisms with acute leukemia risk in children while no association with adults.GST null allele distribution and its association with ALL.The current study reports no association of either GSTM1 null, GSTT1 null, and GSTM1/GSTT1 double null genotypes with ALL in adult patients from Pakistan. ALL risk may not only be affected by genetic factors but also with environmental factors. Therefore, studies with a better study design and a larger sample size including environmental exposure data in addition to genetic variants of xenobiotic metabolism are required to provide more insight into the etiology of adult ALL.In conclusion, results from the current study suggest no statistically significant association of


Once established in poultry, the virus rapidly spread between turkey and chicken farms in neighboring states. Enhanced biosecurity is required to prevent the introduction and dissemination of HPAIV across the poultry industry.Eurasia highly pathogenic avian influenza virus (HPAIV) H5 clade 2.3.4.4 emerged in North America at the end of 2014 and caused outbreaks affecting >50 million poultry in the United States before eradication in June 2015. We investigated the underlying ecologic and epidemiologic processes associated with this viral spread by performing a comparative genomic study using 268 full-length genome sequences and data from outbreak investigations. Reassortant HPAIV H5N2 circulated in wild birds along the Pacific flyway before several spillover events transmitting the virus to poultry farms. Our analysis suggests that  Highly pathogenic avian influenza virus (HPAIV) A(H5N1) emerged in 1996 in Guangdong, China (A/goose/Guangdong/1/1996 [Gs/GD]), and has since caused outbreaks in poultry, infections in wild birds, and often fatal clinical cases in humans in >80 countries . ThiWe sequenced and analyzed the full-length genome sequences of 249 H5N2 and 19 H5N8 HPAIVs collected during the 2014–2015 outbreaks in the United States. Viruses came from 32 wild birds, 7 raptors, 14 backyard poultry farms, and 196 commercial poultry sites. We used a molecular epidemiologic approach involving genome sequences and outbreak information to determine the evolution and spread patterns of these viruses.The National Animal Health Laboratory Network conducts PCR testing for avian influenza in the United States, and per title 9, Code of Federal Regulations, nonnegative samples are forwarded to the National Veterinary Services Laboratories  for confirmation testing and genome sequencing. In December 2014, interagency wild bird surveillance started including testing for the HPAIV Gs/GD lineage in wild birds in the Pacific flyway, and by summer 2015, surveillance was further expanded to include testing for this virus in all flyways (http://www.dnastar.com/t-nextgen-seqman-ngen.aspx). We deposited nucleotide sequences in GenBank . We synthesized complementary DNA and amplified all 8 segments by reverse transcription PCR using SuperScript III  ( GenBank  Table 5.http://platform.gisaid.org) and sequenced the 249 viruses from the United States. In all, 32 viruses were from wild waterfowl in 10 states ; 7 viruses were from captive and wild raptors in 5 states ; and 210 viruses were from backyard and commercial poultry farms in 13 states . Data from Minnesota  and Iowa , where most commercial poultry were affected, predominated in this sample.Of the 265 H5N2 sequences analyzed, we retrieved the 16 viruses from Canada from the GISAID EpiFlu database (https://www.tableau.com/).To demonstrate the phylogenetic organization of the HPAIV outbreak, we built a maximum-likelihood phylogenetic tree of the concatenated genome  with RAxML version 8.0.0 (http://www.fluxus-engineering.com/sharenet_rn.htm) with epsilon set to 0   of HPAIV hemagglutinin (HA) sequences from Asia, Europe, and North America, we tested whether the HPAIV H5 outbreak in North America resulted from a single virus introduction or multiple virus introductions into the bird population of North America. We then developed a more refined model to estimate viral diffusion and transmission between wild and domestic populations and assess the most likely route of spread. We incorporated HPAIV HA sequences from the US and Canada 2014–2015 outbreaks  to investigate the relatedness of isolates Figure 2.Both group 1 and 2 viruses were found in wild birds and gallinaceous poultry  Figure 3Our phylogenetic analysis suggests that the outbreak in the Midwest was initiated through multiple independent HPAIV H5N2 introductions with group 1 viruses of wild bird origin , 3. To fBayesian simulation results showed that turkey farms and chicken farms were equally supported as the source of infection of domestic flocks after establishment of the virus in Midwest US farms . AlthougWe identified 14 common substitutions across the entire genome of HPAIV H5N2 when comparing with US index virus A/northern pintail/WA/40964/2014 (H5N2). These substitutions include 10 nonsynonymous substitutions in group 1 and 2 viruses  and 4 nonsynonymous substitutions in group 2 viruses   Table 3.Phylogenetic reconstruction of source–sink dynamics supports multiple independent introductions of HPAIV H5N8 into the United States during late 2014 from wild birds. Despite the frequent detection of HPAIV H5 in wild birds of the Pacific flyway up to February 2015 , and epidemiologic links could not be found between Pacific Coast and Midwest farms for any virus subgroup. The widespread detection of the HPAIV H5 lineage in healthy wild birds  to infect chickens; directly inoculated and in-contact exposed survivors did not seroconvert (50 of H5N2 group 2 viruses for poultry (103.2–3.6 EID50) was lower than that of group 1 viruses for poultry (105.1 EID50) and index wild birds (105.7 EID50).The epidemiology of the HPAIV H5 detections and pathobiologic features suggest that the early H5N8 and H5N2 group 1 viruses detected in the United States were highly adapted to waterfowl and poorly adapted to chickens and turkeys  were identified among H5N2 group 2 viruses from the United States and a virus isolate from a chicken in British Columbia  reemerged and caused outbreaks in wild birds and domestic poultry across Europe, Asia, and Africa  A(H5Nx) clade 2.3.4.4 isolates from 2014–2015 outbreak in North America.


How to cite this article: Aquino MC, Lim D, Chew PTK. Micropulse P3™(MP3) Laser for Glaucoma: An Innovative Therapy. J Curr Glaucoma Pract 2018;12(2):51-52. Laser therapy remains a useful, noninvasive option in the widening array of glaucoma treatment modalities.Traditional ciliary body lasers are generally cyclodestructive and concern about its use stem from the risks of sight threatening sequelae. Transcleral diode laser cyclophotocoagulation (TSCPC)  is a tre1 It is hypothesized that this form of ciliary body treatment lowers intraocular pressure (IOP) by enhancement of existing uveoscleral outflow channels without photocoagulating the target site.A new form of ciliary body laser termed micropulse P3™ (MP3) using 810 nm infrared diode has been developed. It uses a novel probe design (micropulse P3™ glaucoma device)  of a bal2 and randomized3 studies on advanced, refractory glaucomas have provided evidence that MP3 lowers IOP by an average of 45% from baseline with minimal to nil complications without any incidence of hypotony and phthisis bulbi after 18 months of follow-up. With the micropulse laser machine set at 31.3% duty cycle  the desired effect is reached. Reports on MP3 by other investigators adapting the technology demonstrated the same efficacy. Williams, Moster et al.4 treated patients with refractory glaucoma and reported up to 51% IOP reduction at the last follow-up (7.8 months ± 4.5). Maslin and Noecker5 reported their experience after 12 months of follow-up and found an average of 41.6% IOP reduction without any hypotony. Radcliffe et al.6 observed a mean IOP reduction of 29.8% after 3 months. To show the non destructive effects of MP3 on the ciliary body, Shan Lin et al.7 performed ultrasound biomicroscopic imaging before and after treatment. No ultrasonographic evidence of morphological changes, destruction of adjacent structures nor suprachoroidal effusion were seen following the using of MP3. With encouraging results in lowering IOP, proven safety in advanced and medically refractory glaucoma, MP3 use and its clinical applications continue to be widen.Micropulse technology in glaucoma therapy has paved the way for an efficient and safe procedure applicable to all glaucoma types. The pioneering work and experience of Chew et al. both in the pilot89 New treatment protocols are being evaluated to address cases with minimal or no response to initial MP3. Its role as a potential replacement or adjunct to medical therapy is currently being evaluated. MP3 is now being increasingly used in combination with cataract surgery. MP3 as a temporizing therapy to lower IOP prior to glaucoma filtering surgery in medically refractory cases increases the safety and reduces the risks of devastating sight threatening complications (such as hypotonous maculopathy) before definitive glaucoma filtering surgeries especially in eyes with extremely high IOP preoperatively. Like all new technology, the expanding indications of MP3 remain to be explored.MP3 is increasingly used by eye surgeons in different centers worldwide. Modifications to the power, treatment duration, duty cycle or a combination of the three parameters have been described in the literature.


The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1 and mTORC2 activities were time-of-day dependent. CR induced mTORC1 activity at one time, reduced at two times and has no effect during other times. CR induced mTORC2 activity at one time of the day and has no effects at other times. Circadian clocks are implemented in the regulation of mTOR signaling in mammals and mechanisms of CR. We assayed the effect of CR on mTOR signaling in the liver of mice deficient for circadian transcriptional regulators BMAL1 and CRYs. The CR induced suppression of mTORC1 activity was observed in both clock mutants, while up regulation of mTORC2 was observed in the liver of CRY deficient but not in the liver of BMAL1 deficient mice. Our finding revealed that CR has different time dependent effect on the activity of mTOR complexes 1 and 2 and suggest that circadian clock protein BMAL1 is involved in the up regulation of mTORC2 upon CR in mammals. Calorie restriction (CR) is a feeding regimen that increases longevity in organisms from yeast to primates . The mecThe activity of mTORC1 and mTORC2 is regulated by nutrients, hormones and growth factors . In mammAd Libitum (AL group) access to the food. CR mice received the food at ZT14 . We and others previously reported that feeding CR mice at ZT14 (or ZT12) did not significantly shift the phases of expression of core circadian clock genes [To assess the effect of CR on mTOR signaling, we compared daily rhythms mTORC1 and mTORC2 activities in the liver of mice that were subject to 30% CR for 2 months (CR group) with the activities in the liver of mice that had ck genes ,19–23 in-/-Bmal1 and -/-Cry1,2 mice [-/-Cry1,2 mice but not in in -/-Bmal1 mice. Thus, the circadian clock proteins BMAL1 and CRYs are not required for CR mediated down regulation of mTORC1 activity during rest/fasting period.mTORC1 activity was assayed based on the phosphorylation of ribosomal protein S6 on S235/236 sites (S6 is not a direct target but it is often used as a surrogate marker of mTORC1 activity) ,5 in the-/- mice –26 under-/-Bmal1 mice with high level at ZT10-18. In contrast to the effect in wild type mice CR did not induce mTORC2 activity but resulted in significant reduction at ZT10-14. mTORC2 responded differently to CR in the liver -/-Cry1,2 mice: the phosphorylation of AKT-S473 was reduced at ZT6/ZT10 and increased at ZT14/ZT18. Thus, circadian clock protein BMAL1 but not CRYs is important for the CR mediated induction in mTORC2 activity.We assayed mTORC2 activity through phosphorylation of its downstream target AKT on S473 . Results-/-Bmal1 at ZT10 and ZT14. The phosphorylation was increased at ZT18 and decreased at ZT10 in -/-Cry1,2 mice. Thus, we observed a good correlation between AKT and PRAS40 phosphorylation.TORC2-dependent phosphorylation of AKT stimulates the kinase activity, and we decided to check the effect of CR on the phosphorylation of PRAS40 at S246, it is known that this site is phosphorylated by AKT . We assaWe reported here that CR affected daily changes in mTORC1 and mTORC2 activity in the liver. mTOR plays an important role in the control of metabolism and aging. High mTORC1 activity promotes aging and suppression of mTORC1 increases longevity. mTORC2 might also be involved in the control of longevity but, in contrast to mTORC1, it might be a positive regulator of longevity . Changes-/-Bmal1 and at ZT14 in -/-Cry1,2 mice; mTORC2 activity was high at ZT22 in wild type, intermediate in -/-Bmal1 and low in -/-Cry1,2 mice. Together that suggests that the change in feeding pattern is not the only regulator of CR induced effects on mTOR signaling.It is important to mention that feeding is a regulator of mTOR activity and CR can change a feeding pattern, therefore, some of the observed effects can be due to the changes in the feeding. It is also well documented that phases of clock gene expression in the liver are strongly affected by time of the feeding . Feeding-/-Bmal1 mice [-/-Cry1,2 mice consume about 15% less food [-/-Bmal1 and did not changed in -/-Cry1,2 mice. Thus, the difference in the response of mTOR complexes to CR between wild type and mutants cannot be explained through the difference in total food intake: wild type and -/-Bmal1 mice have the same food intake but different responses.Difference in the amount of the food consumption between wild type and mutants might be another contributing factor. There is no significant difference in food consumption between wild type -/- mice , while Cess food . We comp-/-Bmal1 became rhythmic under CR, while -/-Cry1,2 did not. mTORC2 activity was rhythmic under AL in wild type and -/-Bmal1 mice, it lost the rhythms in wild type under CR but it was still rhythmic in -/-Bmal1 mice. The peaks in mTORC1 and mTORC2 activities coincided at ZT14 for AL wild type mice, while mTORC1 peaked at ZT 16 and mTORC2 peaked at ZT 20  in the liver of -/-Cry1,2mice. Interestingly, at wildness, animals do not have continuous access to the food and our data suggest that intact circadian clock is necessary for temporal separation of the peaks in mTORC1 and mTORC2 activities under conditions of limited nutrients supply.mTORC1 and mTORC2 share the same catalytic subunit, the TOR kinase ,5. It waat ZT 20  in CR wi-/-Bmal1 mice, suggesting that BMAL1 has some clock independent functions in CR. Indeed, CR regulated expression and activity of the clock transcriptional factor BMAL1 is necessary for the regulation of CR-controlled signaling pathways and for the full benefits of CR. Interestingly, while -/-Bmal1 mice demonstrate multiple metabolic abnormalities as well as accelerated aging and reduced lifespan [Based on the presented data, we proposed the following hypothesis: the balance between the complexes established under AL feeding was changed by CR and shifted toward mTORC2. Circadian clock and circadian clock proteins contributed to this shift through compartmentalization of mTORC1 and mTORC2 activities in time. The effect of CR was further compromised in lifespan , this phlifespan . BMAL1 ilifespan ,14 and alifespan  activiti-/-Bmal1 and -/-Cry1,2 mice were previously described [Ad libitum (AL) group had unrestricted access to food. Animals on Caloric restriction (CR) diet received their food once per day at ZT14. CR was started at 3 months of age. Animals were on 30% CR for two months before tissue collection. All groups had unrestricted access to water. All tissue collection experiments were performed for 5-month-old wild type, -/-Bmal1 and -/-Cry1,2 mice. All animal studies were conducted in accordance with the regulations of the Committee on Animal Care and Use at Cleveland State University.Wild type and circadian mutant mice were on C57BL/6J background. escribed ,25. AnimoC. For quantitative analysis, liver samples were run individually to estimate variability between biological replicates. For a representative WB, liver lysates from three different mice were pooled together for each time point. Lysates were prepared with lysis buffer with Protease/Phosphatase Inhibitor Cocktail  using a sonicator. Protein concentration was determined using Bradford protein assay kit. Protein loading was checked by Ponceau staining. List of primary antibodies is in Analysis of protein expression was performed on liver tissues collected every four hours around the clock and stored at -80At least 3 animals for every time point, for each feeding type and for each genotype were used for all experiments. Data are shown as average +/- standard deviation. IBM SPSS Statistics 20 and GraphPad software packages were used for analysis. The effect of diet (AL versus CR) and time of day were tested for significance with two-way repeated ANOVA corrected for multiple comparison using Bonferroni. P<0.05 was considered as statistically significant difference.Supplementary Table 1Supplementary Table 2


Ortega et al. published a comprehensive review which examines the relationship between nutritional genomics and Type 2 diabetes mellitus (T2DM) from a wide perspective . The autPPAR-γ gene is localized in the chromosome 3p25.2 region. The most studied, prevalent and also benign Pro12Ala variant was identified in the PPARG2 isoform [GNGT1) gene localized in the region 7q21.3 [PPAR-γ gene is localized in the region 3p25.2 and the rs number of the Pro12Ala variant is rs1801282 [Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptor subfamily which modulate energy metabolism and act as ligand activated transcription factors by small lipophilic molecules to regulate gene expression ,3. PPAR- isoform . It is k isoform . In a st isoform . It has  isoform . In addin 7q21.3 . The PPAs1801282 .CLOCK variant sampled in both text and Table 3 is incorrect. The authors cited a PREDIMED study by Corella et al. [TCF7L2 and obesity in T2DM. The correct reference seems to be another PREDIMED study performed by the same group [CLOCK rs4580704, CRY1 rs2287161 variants in T2DM, but other circadian related gene variants were not addressed. In a study investigating the gene–diet interactions of the CLOCK variants in metabolic syndrome patients, it was found that TT carriers of rs1801260 variant had higher insulin sensitivity, lower plasma insulin concentration and lower HOMA-IR after one year of low fat consumption [Ortega et al. also mentioned gene–diet interactions related to variants of circadian related genes in T2DM. It is known that the circadian clock is involved in the control of metabolic functions and regulation of blood glucose concentration . In an ea et al.  investigme group . The autsumption . Each 1%sumption . CLOCK variant. In this study, it was quoted that obesity status should be taken into consideration when classifying patients to obtain more accurate information about an interaction between diet and TCF7L2 rs7903146 variant for T2DM risk [Additionally, there is no information in the text about the PREDIMED study, which is associated with TCF7L2–diet interactions, given as reference incorrectly for the 2DM risk .This review successfully discussed the relationship between nutritional genomics and T2DM in light of current data in detail. Readers could obtain more accurate data with considering the aforementioned issues.